ORCID Profile
0000-0002-5958-4181
Current Organisation
University of South Australia
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Publisher: Proceedings of the National Academy of Sciences
Date: 23-11-1999
Abstract: In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is α + -thalassemia. Interestingly, recent epidemiological surveys have demonstrated that α + -thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that α + -thalassemia may facilitate so-called “benign” Plasmodium vivax infection to act later in life as a “natural vaccine” against severe Plasmodium falciparum malaria. Here, in a P. vivax -endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of α + -thalassemia ≥0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a−b−]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous in iduals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous ( FY*A/FY*A null ) and homozygous ( FY*A/FY*A ) in iduals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*A null (2/23 = 0.087) in iduals (odds ratio = 2.05, 95% confidence interval = 0.47–8.91). Emergence of FY*A null in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise α + -thalassemia/ P. vivax -mediated protection against severe P. falciparum malaria.
Publisher: Frontiers Media SA
Date: 16-06-2021
Abstract: Salinity is a major contributing factor to the degradation of arable land, and reductions in crop growth and yield. To overcome these limitations, the breeding of crop varieties with improved salt tolerance is needed. This requires effective and high-throughput phenotyping to optimize germplasm enhancement. Safflower ( Carthamus tinctorius L.), is an underappreciated but highly versatile oilseed crop, capable of growing in saline and arid environments. To develop an effective and rapid phenotyping protocol to differentiate salt responses in safflower genotypes, experiments were conducted in the automated imaging facility at Plant Phenomics Victoria, Horsham, focussing on digital phenotyping at early vegetative growth. The initial experiment, at 0, 125, 250, and 350 mM sodium chloride (NaCl), showed that 250 mM NaCl was optimum to differentiate salt sensitive and tolerant genotypes. Phenotyping of a erse set of 200 safflower genotypes using the developed protocol defined four classes of salt tolerance or sensitivity, based on biomass and ion accumulation. Salt tolerance in safflower was dependent on the exclusion of Na + from shoot tissue and the maintenance of K + uptake. Salinity response identified in glasshouse experiments showed some consistency with the performance of representatively selected genotypes tested under sodic field conditions. Overall, our results suggest that digital phenotyping can be an effective high-throughput approach in identifying candidate genotypes for salt tolerance in safflower.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2011
DOI: 10.1038/MP.2011.158
Abstract: Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippoc us that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.
Publisher: Cold Spring Harbor Laboratory
Date: 18-03-2023
DOI: 10.1101/2023.03.17.533145
Abstract: The sympathetic nervous system controls a wide spectrum of bodily functions including operation of vessels, cardiac rhythm, and the “flight or fight response”. Sympathetic neurons, which are neural crest-derived, develop in coordination with presynaptic motor nerves extending from the central nervous system (CNS). By using nerve-selective genetic ablations, we revealed that sympathetic ganglia development depends on CNS-derived motor innervation. In the absence of preganglionic motor nerves, trunk sympathetic chain ganglia were fragmented and smaller in size, while cervical ganglia were severely misshapen. Sympathetic neurons were misplaced along sensory fibers and projected towards abnormal paths, in some cases invading the sensory dorsal root ganglia. The misplaced progenitors of sympathoblasts corresponded to the nerve-associated, neural crest-derived Schwann cell precursors (SCPs). Notably, we found that SCPs activate the autonomic marker PHOX2B while migrating along motor nerves towards the region of the dorsal aorta in wildtype embryos, suggesting that SCP differentiate into sympathetic neurons while still nerve-associated in motor-ablated embryos. Ligand-receptor prediction from single cell transcriptomic data coupled with functional studies identified Semaphorin 3A/3F as candidate motor nerve-derived signals influencing neural crest migration along axons. Thus, motor nerves control the placement of sympathoblasts and their subsequent axonal navigation during critical periods of sympathetic chain development.
Publisher: Elsevier BV
Date: 2001
Publisher: Elsevier BV
Date: 05-2023
Publisher: Elsevier
Date: 2014
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.YDBIO.2015.04.022
Abstract: The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway regulates many cellular functions including proliferation, migration, survival and protein synthesis. Somatic mutations in PIK3CA, the gene encoding the p110α catalytic subunit of PI3K enzyme, are commonly associated with many human cancers as well as recently being implicated in human overgrowth syndromes. However, it is not clear if such mutations can be inherited through the germline. We have used a novel mouse model with Cre recombinase (Cre)-conditional knock-in of the common H1047R mutation into the endogenous Pik3ca gene. Heterozygous expression of the Pik3ca(H1047R) mutation in the developing mouse embryo resulted in failed 'turning' of the embryo and disrupted vascular remodelling within the embryonic and extraembryonic tissues, leading to lethality prior to E10. As vascular endothelial growth factor A (VEGF-A) signalling was disrupted in these embryos, we used Cre under the control of the Tie2 promoter to target the Pik3ca(H1047R) mutation specifically to endothelial cells. In these embryos turning occurred normally but the vascular remodelling defects and embryonic lethality remained, likely as a result of endothelial hyperproliferation. Our results confirm the lethality associated with heterozygous expression of the Pik3ca(H1047R) mutation during development and likely explain the lack of inherited germline PIK3CA mutations in humans.
Publisher: Springer Science and Business Media LLC
Date: 24-07-2015
DOI: 10.1038/SREP12434
Abstract: Sequencing and expression analyses implicate 14-3-3ζ as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3ζ −/− mice in the Sv/129 background display schizophrenia-like defects. As epistatic interactions play a significant role in disease pathogenesis we generated a new congenic strain in the BALB/c background to determine the impact of genetic interactions on the 14-3-3ζ −/− phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3ζ −/− BALB/c mice identified enlarged lateral ventricles, reduced synaptic density and ectopically positioned pyramidal neurons in all subfields of the hippoc us. In contrast to our previous analyses, 14-3-3ζ −/− BALB/c mice lacked locomotor hyperactivity that was underscored by normal levels of the dopamine transporter (DAT) and dopamine signalling. Taken together, our results demonstrate that dysfunction of 14-3-3ζ gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3ζ-deficient BALB/c mice therefore provide a novel model to address the underlying biology of structural defects affecting the hippoc us and ventricle and cognitive defects such as hippoc al-dependent learning and memory.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2021
DOI: 10.1186/S12915-021-01014-3
Abstract: The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system. The RP, in turn, constitutes a patterning center for dorsal interneuron development. The factors underlying establishment of the definitive RP and its segregation from NC and dorsal interneurons are currently unknown. We performed a transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity, both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population. Collectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.
Publisher: MDPI AG
Date: 23-11-2020
Abstract: Genomic selection can increase the rate of genetic gain in crops through accumulation of positive alleles and reduce phenotyping costs by shortening the breeding cycle time. We performed genomic prediction for resistance to wheat rusts in tetraploid wheat accessions using three cross-validation with the objective of predicting: (1) rust resistance when in iduals are not tested in all environments/locations, (2) the performance of lines across years, and (3) adult plant resistance (APR) of lines with bivariate models. The rationale for the latter is that seedling assays are faster and could increase prediction accuracy for APR. Predictions were derived from adult plant and seedling responses for leaf rust (Lr), stem rust (Sr) and stripe rust (Yr) in a panel of 391 accessions grown across multiple years and locations and genotyped using 16,483 single nucleotide polymorphisms. Different Bayesian models and genomic best linear unbiased prediction yielded similar accuracies for all traits. Site and year prediction accuracies for Lr and Yr ranged between 0.56–0.71 for Lr and 0.51–0.56 for Yr. While prediction accuracy for Sr was variable across different sites, accuracies for Yr were similar across different years and sites. The changes in accuracies can reflect higher genotype × environment (G × E) interactions due to climate or pathogenic variation. The use of seedling assays in genomic prediction was underscored by significant positive genetic correlations between all stage resistance (ASR) and APR (Lr: 0.45, Sr: 0.65, Yr: 0.50). Incorporating seedling phenotypes in the bivariate genomic approach increased prediction accuracy for all three rust diseases. Our work suggests that the underlying plant-host response to pathogens in the field and greenhouse screens is genetically correlated, but likely highly polygenic and therefore difficult to detect at the in idual gene level. Overall, genomic prediction accuracies were in the range suitable for selection in early generations of the breeding cycle.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2021
DOI: 10.1007/S00122-021-03809-Y
Abstract: Several stable QTL were detected using metaGWAS analysis for different agronomic and quality traits under 26 normal and heat stressed environments. Heat stress, exacerbated by global warming, has a negative influence on wheat production worldwide and climate resilient cultivars can help mitigate these impacts. Selection decisions should therefore depend on multi-environment experiments representing a range of temperatures at critical stages of development. Here, we applied a meta-genome wide association analysis (metaGWAS) approach to detect stable QTL with significant effects across multiple environments. The metaGWAS was applied to 11 traits scored in 26 trials that were sown at optimal or late times of sowing (TOS1 and TOS2, respectively) at five locations. A total of 2571 unique wheat genotypes (13,959 genotypes across all environments) were included and the analysis conducted on TOS1, TOS2 and both times of sowing combined (TOS1 ). The germplasm was genotyped using a 90 k Infinium chip and imputed to exome sequence level, resulting in 341,195 single nucleotide polymorphisms (SNPs). The average accuracy across all imputed SNPs was high (92.4%). The three metaGWAS analyses revealed 107 QTL for the 11 traits, of which 16 were detected in all three analyses and 23 were detected in TOS1 only. The remaining QTL were detected in either TOS1 or TOS2 with or without TOS1 , reflecting the complex interactions between the environments and the detected QTL. Eight QTL were associated with grain yield and seven with multiple traits. The identified QTL provide an important resource for gene enrichment and fine mapping to further understand the mechanisms of gene × environment interaction under both heat stressed and unstressed conditions.
Publisher: MDPI AG
Date: 25-10-2023
Publisher: The Company of Biologists
Date: 06-2009
DOI: 10.1242/DEV.034322
Abstract: The peripheral nervous system (PNS) of higher vertebrates is segmented to align the spinal nerve roots with the vertebrae. This co-patterning is set up during embryogenesis, when vertebrae develop from the sclerotome layer of the metameric somites, and PNS neurons and glia differentiate from neural crest cells (NCCs) that preferentially migrate into the anterior sclerotome halves. Previous analyses of mice deficient in the class 3 semaphorin (SEMA3)receptors neuropilin (NRP) 1 or 2 raised the possibility that each controlled a distinct aspect of trunk NCC migration. We now demonstrate that both pathways act sequentially in distinct NCC subpopulations and thereby cooperate to enforce segmental NCC migration. Specifically, SEMA3A/NRP1 signalling first directs one population of NCCs from the intersomitic path into the sclerotome,and SEMA3F/NRP2 signalling acts subsequently to restrict a second population to the anterior half of the sclerotome. NCC exclusion from either the posterior sclerotome or the intersomitic boundary is sufficient to enforce the separation of neighbouring NCC streams and the segregation of sensory NCC progeny into metameric dorsal root ganglia (DRG). By contrast, the combined loss of both guidance pathways leads to ectopic invasion of the intersomitic furrows and posterior sclerotome halves, disrupting metameric NCC streaming and DRG segmentation.
Publisher: IOP Publishing
Date: 12-03-2002
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.YDBIO.2011.12.032
Abstract: During lymphangiogenesis in the mammalian embryo, a subset of vascular endothelial cells in the cardinal veins is reprogrammed to adopt a lymphatic endothelial fate. The prevailing model of lymphangiogenesis contends that these lymphatic precursor cells migrate away from the cardinal veins and reassemble peripherally as lymph sacs from which a lymphatic vasculature is generated. However, this model fails to account for a number of observations that, as a result, have remained anecdotal. Here, we use optical projection tomography, confocal microscopy and in vivo live imaging to uncover three key stages of lymphatic vascular morphogenesis in the mouse embryo at high resolution. First, we define territories or "pre-lymphatic clusters" of Prox1-positive lymphatic endothelial progenitor cells along the antero-posterior axis of the cardinal veins. Second, these pre-lymphatic clusters undergo progressive extrusion ("ballooning") to generate primitive lymph sacs. Third, lymphatic vessels emerge by a combination of mechanisms including sprouting from the lymph sacs and direct delamination of streams of cells from the cardinal veins. Our data support a new model for lymphatic vascular patterning and morphogenesis, as a basis for identifying the molecular cues governing these processes.
Publisher: Hindawi Limited
Date: 11-07-2016
DOI: 10.1002/HUMU.23032
Abstract: Ectrodactyly/split hand-foot malformation is genetically heterogeneous with more than 100 syndromic associations. Acinar dysplasia is a rare congenital lung lesion of unknown etiology, which is frequently lethal postnatally. To date, there have been no reports of combinations of these two phenotypes. Here, we present an infant from a consanguineous union with both ectrodactyly and autopsy confirmed acinar dysplasia. SNP array and whole-exome sequencing analyses of the affected infant identified a novel homozygous Fibroblast Growth Factor Receptor 2 (FGFR2) missense mutation (p.R255Q) in the IgIII domain (D3). Expression studies of Fgfr2 in development show localization to the affected limbs and organs. Molecular modeling and genetic and functional assays support that this mutation is at least a partial loss-of-function mutation, and contributes to ectrodactyly and acinar dysplasia only in homozygosity, unlike previously reported heterozygous activating FGFR2 mutations that cause Crouzon, Apert, and Pfeiffer syndromes. This is the first report of mutations in a human disease with ectrodactyly with pulmonary acinar dysplasia and, as such, homozygous loss-of-function FGFR2 mutations represent a unique syndrome.
Publisher: Wiley
Date: 02-11-2020
DOI: 10.1002/TPG2.20064
Abstract: Safflower, a minor oilseed crop, is gaining increased attention for food and industrial uses. Safflower genebank collections are an important genetic resource for crop enhancement and future breeding programs. In this study, we investigated the population structure of a safflower collection sourced from the Australian Grain Genebank and assessed the potential of genomic prediction (GP) to evaluate grain yield and related traits using single and multi‐site models. Prediction accuracies (PA) of genomic best linear unbiased prediction (GBLUP) from single site models ranged from 0.21 to 0.86 for all traits examined and were consistent with estimated genomic heritability ( h 2 ), which varied from low to moderate across traits. We generally observed a low level of genome × environment interactions (g × E). Multi‐site g × E GBLUP models only improved PA for accessions with at least some phenotypes in the training set. We observed that relaxing quality filtering parameters for genotype‐by‐sequencing (GBS), such as missing genotype call rate, did not affect PA but upwardly biased h 2 estimation. Our results indicate that GP is feasible in safflower evaluation and is potentially a cost‐effective tool to facilitate fast introgression of desired safflower trait variation from genebank germplasm into breeding lines.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2017
DOI: 10.1186/S12861-017-0147-Z
Abstract: Cranial neural crest cells (NCCs) are a unique embryonic cell type which give rise to a erse array of derivatives extending from neurons and glia through to bone and cartilage. Depending on their point of origin along the antero-posterior axis cranial NCCs are rapidly sorted into distinct migratory streams that give rise to axial specific structures. These migratory streams mirror the underlying segmentation of the brain with NCCs exiting the diencephalon and midbrain following distinct paths compared to those exiting the hindbrain rhombomeres (r). The genetic landscape of cranial NCCs arising at different axial levels remains unknown. Here we have used RNA sequencing to uncover the transcriptional profiles of mouse cranial NCCs arising at different axial levels. Whole transcriptome analysis identified over 120 transcripts differentially expressed between NCCs arising anterior to r3 (referred to as r1-r2 migratory stream for simplicity) and the r4 migratory stream. Eight of the genes differentially expressed between these populations were validated by RT-PCR with 2 being further validated by in situ hybridisation. We also explored the expression of the Neuropilins ( Nrp1 and Nrp2 ) and their co-receptors and show that the A-type Plexins are differentially expressed in different cranial NCC streams. Our analyses identify a large number of genes differentially regulated between cranial NCCs arising at different axial levels. This data provides a comprehensive description of the genetic landscape driving ersity of distinct cranial NCC streams and provides novel insight into the regulatory networks controlling the formation of specific skeletal elements and the mechanisms promoting migration along different paths.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2014
Publisher: Elsevier BV
Date: 09-2012
Publisher: MDPI AG
Date: 19-01-2021
DOI: 10.3390/BIOM11010128
Abstract: Vascular endothelial growth factor A (VEGF-A or VEGF) is a highly conserved secreted signalling protein best known for its roles in vascular development and angiogenesis. Many non-endothelial roles for VEGF are now established, with the discovery that VEGF and its receptors VEGFR1 and VEGFR2 are expressed in many non-vascular cell-types, as well as various cancers. In addition to secreted VEGF binding to its receptors in the extracellular space at the cell membrane (i.e., in a paracrine or autocrine mode), intracellularly localised VEGF is emerging as an important signalling molecule regulating cell growth, survival, and metabolism. This intracellular mode of signalling has been termed “intracrine”, and refers to the direct action of a signalling molecule within the cell without being secreted. In this review, we describe ex les of intracrine VEGF signalling in regulating cell growth, differentiation and survival, both in normal cell homeostasis and development, as well as in cancer. We further discuss emerging evidence for the molecular mechanisms underpinning VEGF intracrine function, as well as the implications this intracellular mode of VEGF signalling may have for use and design of anti-VEGF cancer therapeutics.
Publisher: The Company of Biologists
Date: 2016
DOI: 10.1242/DEV.130922
Abstract: Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects both during early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model by which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation toward differentiation in the growing eye.
Publisher: Springer US
Date: 16-12-2022
DOI: 10.1007/978-1-0716-1847-9_16
Abstract: Ex vivo explant models are a valuable tool for analyzing organ and tissue morphogenesis, providing the opportunity to manipulate and interrogate specific cellular and/or molecular pathways that may not be possible using conventional methods in vivo. The mandible primordia is a remarkably self-organizing structure that has the ability to develop cartilage, bone, teeth, epithelial tissue, and the tongue when grown in culture ex vivo and closely mimics the development of these structures in vivo. Here we describe a robust protocol for the culture of mandibular explants using serum-free, chemically defined culture media. We also describe methods for manipulating mandible and/or Meckel's cartilage development by implantation of agarose beads soaked in various molecular factors to augment mandible development, as well as methods for Alcian blue staining of Meckel's cartilage and immunohistochemistry. This culture method can also be adapted for other molecular analyses, including addition of small-molecule inhibitors and/or growth factors to the culture media, as well as culturing explants from genetically modified mice.
Publisher: Informa UK Limited
Date: 04-2010
Publisher: MDPI AG
Date: 29-06-2023
Abstract: Global barley production is threatened by plant pathogens, especially the rusts. In this study we used a targeted genotype-by-sequencing (GBS) assisted GWAS approach to identify rust resistance alleles in a collection of 287 genetically distinct erse barley landraces and historical cultivars available in the Australian Grains Genebank (AGG) and originally sourced from Eastern Europe. The accessions were challenged with seven US-derived cereal rust pathogen races including Puccinia hordei (Ph-leaf rust) race 17VA12C, P. coronata var. hordei (Pch-crown rust) race 91NE9305 and five pathogenically erse races of P. striiformis f. sp. hordei (Psh-stripe rust) (PSH-33, PSH-48, PSH-54, PSH-72 and PSH-100) and phenotyped quantitatively at the seedling stage. Novel resistance factors were identified on chromosomes 1H, 2H, 4H and 5H in response to Pch, whereas a race-specific QTL on 7HS was identified that was effective only to Psh isolates PSH-72 and PSH-100. A major effect QTL on chromosome 5HL conferred resistance to all Psh races including PSH-72, which is virulent on all 12 stripe rust differential tester lines. The same major effect QTL was also identified in response to leaf rust (17VA12C) suggesting this locus contains several pathogen specific rust resistance genes or the same gene is responsible for both leaf rust and stripe rust resistance. Twelve accessions were highly resistant to both leaf and stripe rust diseases and also carried the 5HL QTL. We subsequently surveyed the physical region at the 5HL locus for across the barley pan genome variation in the presence of known resistance gene candidates and identified a rich source of high confidence protein kinase and antifungal genes in the QTL region.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 21-02-2020
Publisher: The Company of Biologists
Date: 05-2008
DOI: 10.1242/DEV.015412
Abstract: Neuropilin (NRP) receptors and their class 3 semaphorin (SEMA3) ligands play well-established roles in axon guidance, with loss of NRP1, NRP2, SEMA3A or SEMA3F causing defasciculation and errors in growth cone guidance of peripherally projecting nerves. Here we report that loss of NRP1 or NRP2 also impairs sensory neuron positioning in the mouse head, and that this defect is a consequence of inappropriate cranial neural crest cell migration. Specifically, neural crest cells move into the normally crest-free territory between the trigeminal and hyoid neural crest streams and recruit sensory neurons from the otic placode these ectopic neurons then extend axons between the trigeminal and facioacoustic ganglia. Moreover, we found that NRP1 and NRP2 cooperate to guide cranial neural crest cells and position sensory neurons thus, in the absence of SEMA3/NRP signalling, the segmentation of the cranial nervous system is lost. We conclude that neuropilins play multiple roles in the sensory nervous system by directing cranial neural crest cells,positioning sensory neurons and organising their axonal projections.
Publisher: Proceedings of the National Academy of Sciences
Date: 14-04-2009
Abstract: Neural crest cells (NCCs) are highly motile embryonic stem cells that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways that correlate with NCC fate. The firstborn NCCs travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near the dorsal aorta, while the lastborn NCCs migrate superficially beneath the epidermis to give rise to melanocytes. Yet, most NCCs enter the somites to form the intermediate wave that gives rise to sympathetic and sensory neurons. Here we show that the repulsive guidance cue SEMA3A and its receptor neuropilin 1 (NRP1) are essential to direct the intermediate wave NCC precursors of peripheral neurons from a default pathway alongside intersomitic blood vessels into the anterior sclerotome. Thus, loss of function for either gene caused excessive intersomitic NCC migration, and this led to ectopic neuronal differentiation along both the anteroposterior and dorsoventral axes of the trunk. The choice of migratory pathway did not affect the specification of NCCs, as they retained their commitment to differentiate into sympathetic or sensory neurons, even when they migrated on an ectopic dorsolateral path that is normally taken by melanocyte precursors. We conclude that NRP1 signaling coordinates pathway choice with NCC fate and therefore confines neuronal differentiation to appropriate locations.
Publisher: Elsevier BV
Date: 06-2011
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/DEV.190488
Abstract: Craniofacial development is a complex morphogenic process that requires highly orchestrated interactions between multiple cell types. Blood vessel-derived angiocrine factors are known to promote proliferation of chondrocytes in Meckel's cartilage to drive jaw outgrowth, however the specific factors controlling this process remain unknown. Here, we use in vitro and ex vivo cell and tissue culture, as well as genetic mouse models to identify IGF-1 as a novel angiocrine factor directing Meckel's cartilage growth during embryonic development. We show that IGF-1 is secreted by blood vessels and that deficient IGF-1 signalling underlies mandibular hypoplasia in Wnt1-Cre Vegfafl/fl mice that exhibit vascular and associated jaw defects. Furthermore, conditional removal of IGF-1 from blood vessels causes craniofacial defects including a shortened mandible, and reduced proliferation of Meckel's cartilage chondrocytes. This demonstrates a critical angiocrine role for IGF-1 during craniofacial cartilage growth, and identifies IGF-1 as a putative therapeutic for jaw and/or cartilage growth disorders.
Publisher: MDPI AG
Date: 07-2020
Abstract: Among the rust diseases, leaf rust of wheat caused by Puccinia triticina, is the most prevalent worldwide and causes significant yield losses. This study aimed to determine the genomic location of loci that control adult plant resistance (APR) to leaf rust in the pre-Green Revolution landrace accession, Aus27506, from the “Watkins Collection”. An Aus27506/Aus27229-derived F7 recombinant inbred line (RIL) population was screened under field conditions across three cropping seasons and genotyped with the iSelect 90K Infinium SNP bead chip array. One quantitative trait loci (QTL) on each of the chromosomes 1BL, 2B and 2DL explained most of the leaf rust response variation in the RIL population, and these were named QLr.sun-1BL, QLr.sun-2B and QLr.sun-2DL, respectively. QLr.sun-1BL and QLr.sun-2DL were contributed by Aus27506. QLr.sun-1BL is likely Lr46, while QLr.sun-2DL appeared to be a new APR locus. The alternate parent, Aus27229, carried the putatively new APR locus QLr.sun-2B. The comparison of average severities among RILs carrying these QTL in different combinations indicated that QLr.sun-2B does not interact with either of the other two QTL however, the combination of QLr.sun-1BL and QLr.sun-2DL reduced disease severity significantly. In planta fungal quantification assays validated these results. The RILs carrying QLr.sun-1BL and QLr.sun-2DL did not differ significantly from the parent Aus27506 in terms of resistance. Aus27506 can be used as a source of adult plant leaf rust resistance in breeding programs.
Publisher: Springer Science and Business Media LLC
Date: 05-06-2020
Publisher: American Society of Hematology
Date: 05-08-2010
DOI: 10.1182/BLOOD-2009-12-257832
Abstract: Blood vessel networks expand in a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor (VEGF), which stimulates tip cell protrusion. Yet it is not known which factors promote the fusion of neighboring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signaling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell-surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for antiangiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularization in ischemic disease.
Publisher: Frontiers Media SA
Date: 29-06-2023
DOI: 10.3389/FCELL.2023.1172114
Abstract: Blood vessels are well-known to play roles in organ development and repair, primarily owing to their fundamental function in delivering oxygen and nutrients to tissues to promote their growth and homeostasis. Endothelial cells however are not merely passive conduits for carrying blood. There is now evidence that endothelial cells of the vasculature actively regulate tissue-specific development, morphogenesis and organ function, as well as playing roles in disease and cancer. Angiocrine factors are growth factors, cytokines, signaling molecules or other regulators produced directly from endothelial cells to instruct a erse range of signaling outcomes in the cellular microenvironment, and are critical mediators of the vascular control of organ function. The roles of angiocrine signaling are only beginning to be uncovered in erse fields such as homeostasis, regeneration, organogenesis, stem-cell maintenance, cell differentiation and tumour growth. While in some cases the specific angiocrine factor involved in these processes has been identified, in many cases the molecular identity of the angiocrine factor(s) remain to be discovered, even though the importance of angiocrine signaling has been implicated. In this review, we will specifically focus on roles for endothelial-derived angiocrine signaling in instructing tissue morphogenesis and organogenesis during embryonic and perinatal development.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.YEXCR.2007.09.001
Abstract: The complex mechanisms by which transforming growth factor beta (TGFbeta) regulate re-epithelialisation following injury of stratified epithelia are not fully understood. TGFbeta signals via binding to distinct receptors activating downstream effectors, including Smads which initiate transcription of target genes. However, studies have shown that TGFbeta can also signal independently of Smads through MAPK pathways, demonstrating the ersity of TGFbeta signalling. Connective tissue growth factor (CTGF) is strongly induced by and acts downstream of TGFbeta causing pathophysiology in tissues by inducing matrix deposition, conversion of fibroblasts into contractile myofibroblasts (e.g. dermis and corneal stroma) and stimulation of epithelial-to-mesenchymal transition (e.g. kidney and lung) all of which are known to cause fibrosis. However, a role for CTGF in epithelial cell function which does not involve direct contribution to fibrosis has not been demonstrated. We show for the first time that synthesis of CTGF in cultures of human corneal epithelial cells is induced by TGFbeta through the Ras/MEK/ERK MAPK signalling pathway and that this is required for re-epithelialisation to occur through cell migration. These data reveal a novel function for CTGF in the regulation of epithelial tissue repair beyond its established role in fibrosis, and further highlight the complexity of TGFbeta regulation of epithelial cell function.
Publisher: American Institute of Mathematical Sciences (AIMS)
Date: 2015
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2020
DOI: 10.1101/2020.02.09.940767
Abstract: Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show that gins1 and gins2 mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the GINS complex as neither Gins1 nor Gins2 seem to be present during these stages.
Publisher: Elsevier BV
Date: 10-2014
Publisher: Oxford University Press (OUP)
Date: 18-03-2020
DOI: 10.1093/JXB/ERAA143
Abstract: The development of crop varieties with higher nitrogen use efficiency is crucial for sustainable crop production. Combining high-throughput genotyping and phenotyping will expedite the discovery of novel alleles for breeding crop varieties with higher nitrogen use efficiency. Digital and hyperspectral imaging techniques can efficiently evaluate the growth, biophysical, and biochemical performance of plant populations by quantifying canopy reflectance response. Here, these techniques were used to derive automated phenotyping of indicator biomarkers, biomass and chlorophyll levels, corresponding to different nitrogen levels. A detailed description of digital and hyperspectral imaging and the associated challenges and required considerations are provided, with application to delineate the nitrogen response in wheat. Computational approaches for spectrum calibration and rectification, plant area detection, and derivation of vegetation index analysis are presented. We developed a novel vegetation index with higher precision to estimate chlorophyll levels, underpinned by an image-processing algorithm that effectively removed background spectra. Digital shoot biomass and growth parameters were derived, enabling the efficient phenotyping of wheat plants at the vegetative stage, obviating the need for phenotyping until maturity. Overall, our results suggest value in the integration of high-throughput digital and spectral phenomics for rapid screening of large wheat populations for nitrogen response.
Publisher: IOP Publishing
Date: 03-02-2004
Publisher: Wiley
Date: 23-07-2021
DOI: 10.1111/PCE.14145
Abstract: Genotype‐by‐environment interaction (GEI) is one of the major factors affecting the prediction accuracy of genomic selection (GS) models. Standard models have low power to model complex GEI, and they fail to predict phenotypes in unobserved environments. Here, we developed a novel prediction model that account for GEI, named 3GS, that combines genotype plus genotype × environment (GGE) analysis with GS. The model calculates the principal components (PCs) of the environmental phenotypes using GGE analysis and predict the performance of these PCs using standard GS models before converting the GEBVs of these PCs (pcGEBVs) back to the original phenotypes. We demonstrated three advantages of the new model. First, 3GS showed significantly higher prediction accuracy primarily for deviated environments that have low to negative correlations to other environments. Second, 3GS can predict new genotypes in unobserved environments with high accuracy. Third, the computational complexity of 3GS increases linearly with increasing the number of environments and the population size, unlike the standard models that exhibit exponential increase, making it hundreds of times faster than the standard models for large data sets. 3GS can improve prediction accuracy with minimal resources in modern breeding programmes in which massive populations get multi‐environment phenotypes with high‐throughput techniques.
Publisher: Elsevier BV
Date: 04-2014
Publisher: The Company of Biologists
Date: 10-2011
DOI: 10.1242/DEV.070037
Abstract: Neuropilin 1 (NRP1) is a transmembrane glycoprotein that is essential for blood vessel development in vertebrates. Best known for its ability to bind members of the vascular endothelial growth factor (VEGF) and class 3 semaphorin families through its extracellular domain, it also has a highly conserved cytoplasmic domain, which terminates in a SEA motif that binds the PDZ protein synectin/GIPC1/NIP. Previous studies in zebrafish embryos and tissue culture models raised the possibility that the SEA motif of NRP1 is essential for angiogenesis. Here, we describe the generation of mice that express a form of NRP1 that lacks the cytoplasmic domain and, therefore, the SEA motif (Nrp1cytoΔ/Δ mice). Our analysis of pre- and perinatal vascular development revealed that vasculogenesis and angiogenesis proceed normally in these mutants, demonstrating that the membrane-anchored extracellular domain is sufficient for vessel growth. By contrast, the NRP1 cytoplasmic domain is required for normal arteriovenous patterning, because arteries and veins crossed each other at an abnormally high frequency in the Nrp1cytoΔ/Δ retina, as previously reported for mice with haploinsufficient expression of VEGF in neural progenitors. At crossing sites, the artery was positioned anteriorly to the vein, and both vessels were embedded in a shared collagen sleeve. In human eyes, similar arteriovenous crossings are risk factors for branch retinal vein occlusion (BRVO), an eye disease in which compression of the vein by the artery disrupts retinal blood flow, causing local tissue hypoxia and impairing vision. Nrp1cytoΔ/Δ mice may therefore provide a suitable genetic model to study the aetiology of BRVO.
Publisher: The Company of Biologists
Date: 2016
DOI: 10.1242/DEV.126854
Abstract: The correct migration and axon extension of neurons in the developing nervous system is essential for the appropriate wiring and function of neural networks. Here, we report that O-sulfotransferases, a class of enzymes that modify heparan sulfate proteoglycans (HSPGs), are essential to regulate neuronal migration and axon development. We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST is important to regulate the migration of facial branchiomotor (FBM) neurons in the hindbrain. We have also investigated how HS2ST interacts with other signals in the hindbrain and show that FGF signalling regulates FBM neuron migration in an HS2ST-dependent manner.
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9412-0_12
Abstract: Detailed investigation of the neural crest cell proteome has lingered behind that of the transcriptome due to the challenge of obtaining sufficient starting material for subsequent proteomic investigation. Compounded by the complexity of protein abundance, large number of posttranslational modifications, and the stochastic nature of proteomics approaches, little data so far exists describing the true neural crest cell proteome. However, recent advances in instrument sensitivity and recovery of material during s le preparation have alleviated many of these problems and make proteomics analysis an underutilized tool to study neural crest cell biology. Here we present a quantitative proteomics protocol for deep analysis of both whole proteome and posttranslational modifications and a separate protocol for ultrasensitive proteomic profiling from submicrogram amounts of protein.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2021
DOI: 10.1186/S12920-021-00911-4
Abstract: Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3 . LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1016/S1357-2725(03)00246-2
Abstract: The initial step of the heme biosynthetic pathway in erythroid cells is catalyzed by an erythroid-specific isoform of 5-aminolevulinate synthase-2 (ALAS2). Previously, an alternatively spliced mRNA isoform of ALAS2 was identified although the functional significance of the encoded protein was unknown. We sought to characterize the contribution of this ALAS2 isoform to overall erythroid heme biosynthesis. Here, we report the identification of three novel ALAS2 mRNA splice isoforms in addition to the previously described isoform lacking exon 4-derived sequence. Quantitation of these mRNAs using ribonuclease protection experiments revealed that the isoform without exon 4-derived sequence represents approximately 35-45% of total ALAS2 mRNA while the newly identified transcripts together represent approximately 15%. Despite the significant amounts of these three new transcripts, their features indicate that they are unlikely to substantially contribute to overall mitochondrial ALAS2 activity. In contrast, in vitro studies show that the major splice variant (lacking exon 4-encoded sequence) produces a functional enzyme, albeit with slightly reduced activity and with affinity for the ATP-specific, beta subunit of succinyl CoA synthase, comparable to that of mature ALAS2. It was also established that the first 49 amino acids of the ALAS2 pre-protein are necessary and sufficient for translocation across the mitochondrial inner membrane and that this process is not affected by the absence of exon 4-encoded sequence. We conclude that the major splice isoform of ALAS2 is functional in vivo and could significantly contribute to erythroid heme biosynthesis and hemoglobin formation.
Publisher: The Company of Biologists
Date: 2018
DOI: 10.1242/DEV.162552
Abstract: The adrenal medulla is composed of neuroendocrine chromaffin cells that secrete adrenaline into the systemic circulation to maintain physiological homeostasis and enable the autonomic stress response. How chromaffin cell precursors colonise the adrenal medulla, and how they become connected to central nervous system derived preganglionic sympathetic neurons remains largely unknown. By combining lineage tracing, gene expression studies, genetic ablation and the analysis of mouse mutants, we demonstrate that preganglionic axons direct chromaffin cell precursors into the adrenal primordia. We further show that preganglionic axons and chromaffin cell precursors require class 3 semaphorin (SEMA3) signalling through neuropilins (NRP) to target the adrenal medulla. Thus, SEMA3s serve as guidance cues to control formation of the adrenal neuroendocrine system by establishing appropriate connections between preganglionic neurons and adrenal chromaffin cells that regulate the autonomic stress response.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2017
Abstract: Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early‐onset hypertension in animal models. Examination of sympathetic nerve fiber density of the tonsillar arteries in children undergoing adenotonsillectomy for Sleep disordered breathing will address this question in humans. Thirteen children scheduled for adenotonsillectomy to treat sleep disordered breathing underwent pupillometry, polysomnography, flow‐mediated dilation, resting brachial artery blood flow velocity (velocity time integral), and platelet aggregation. The dorsal lingual artery (tonsil) was stained and immunofluorescence techniques used to determine sympathetic nerve fiber density. Sympathetic nerve fiber density was correlated with increased resting velocity time integral ( r =0.63 P .05) and a lower Neuronal Pupillary Index ( r =−0.71, P .01), as well as a slower mean pupillary constriction velocity (mean, r =−0.64 P .05). A faster resting velocity time integral was associated with a slower peak pupillary constriction velocity ( r =−0.77 P .01) and higher platelet aggregation to collagen antigen ( r =0.64 P .05). Slower mean and peak pupillary constriction velocity were associated with higher platelet aggregation scores ( P .05 P .01, respectively). These results indicate that sympathetic activity is associated with change in both the function and structure of systemic vasculature in children with sleep disordered breathing.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
Publisher: American Physical Society (APS)
Date: 30-04-2004
Publisher: The Company of Biologists
Date: 15-05-2007
DOI: 10.1242/DEV.002402
Abstract: Blood vessels and neurons share several types of guidance cues and cell surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 is present on blood vessels and nerves. NRP1 binds two structurally erse ligands, the semaphorin SEMA3A and the VEGF164 isoform of vascular endothelial growth factor. SEMA3A was originally identified as a repulsive cue for developing axons that acts by signalling through receptor complexes containing NRP1 and plexins. In vitro, SEMA3A also inhibits integrin function and competes with VEGF164 for binding to NRP1 to modulate the migration of endothelial cells. These observations resulted in a widely accepted model of vascular patterning in which the balance of VEGF164 and SEMA3A determines endothelial cell behaviour. However, we now demonstrate that SEMA3A is not required for angiogenesis in the mouse, which instead is controlled by VEGF164. We find that SEMA3A, but not VEGF164, is required for axon patterning of limb nerves, even though the competition between VEGF164 and SEMA3A for NRP1 affects the migration of neuronal progenitor cells in vitro and has been hypothesised to control axon guidance. Moreover, we show that there is no genetic interaction between SEMA3A and VEGF164 during vasculogenesis, angiogenesis or limb axon patterning, suggesting that ligand competition for NRP1 binding cannot explain neurovascular congruence, as previously suggested. We conclude that NRP1 contributes to both neuronal and vascular patterning by preferentially relaying SEMA3A signals in peripheral axons and VEGF164 signals in blood vessels.
Publisher: MDPI AG
Date: 09-01-2023
Abstract: Advanced plant phenotyping techniques to measure biophysical traits of crops are helping to deliver improved crop varieties faster. Phenotyping of plants using different sensors for image acquisition and its analysis with novel computational algorithms are increasingly being adapted to measure plant traits. Thermal and multispectral imagery provides novel opportunities to reliably phenotype crop genotypes tested for biotic and abiotic stresses under glasshouse conditions. However, optimization for image acquisition, pre-processing, and analysis is required to correct for optical distortion, image co-registration, radiometric rescaling, and illumination correction. This study provides a computational pipeline that optimizes these issues and synchronizes image acquisition from thermal and multispectral sensors. The image processing pipeline provides a processed stacked image comprising RGB, green, red, NIR, red edge, and thermal, containing only the pixels present in the object of interest, e.g., plant canopy. These multimodal outputs in thermal and multispectral imageries of the plants can be compared and analysed mutually to provide complementary insights and develop vegetative indices effectively. This study offers digital platform and analytics to monitor early symptoms of biotic and abiotic stresses and to screen a large number of genotypes for improved growth and productivity. The pipeline is packaged as open source and is hosted online so that it can be utilized by researchers working with similar sensors for crop phenotyping.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2019
DOI: 10.1186/S12864-019-6249-1
Abstract: Barley yellow dwarf (BYD) is an important virus disease that causes significant reductions in wheat yield. For effective control of Barley yellow dwarf virus through breeding, the identification of genetic sources of resistance is key to success. In this study, 335 geographically erse wheat accessions genotyped using an Illumina iSelect 90 K single nucleotide polymorphisms (SNPs) bead chip array were used to identify new sources of resistance to BYD in different environments. A genome-wide association study (GWAS) performed using all the generalised and mixed linkage models (GLM and MLM, respectively) identified a total of 36 significant marker-trait associations, four of which were consistently detected in the K model. These four novel quantitative trait loci (QTL) were identified on chromosomes 2A, 2B, 6A and 7A and associated with markers IWA3520, IWB24938, WB69770 and IWB57703, respectively. These four QTL showed an additive effect with the average visual symptom score of the lines containing resistance alleles of all four QTL being much lower than those with less favorable alleles. Several Chinese landraces, such as H-205 (Baimazha) and H-014 (Dahongmai) which have all four favorable alleles, showed consistently higher resistance in different field trials. None of them contained the previously described Bdv2, Bdv3 or Bdv4 genes for BYD resistance. This study identified multiple novel QTL for BYD resistance and some resistant wheat genotypes. These will be useful for breeders to generate combinations with and/or without Bdv2 to achieve higher levels and more stable BYD resistance.
Publisher: The Company of Biologists
Date: 09-2011
DOI: 10.1242/DEV.063362
Abstract: Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.
Publisher: MDPI AG
Date: 22-06-2023
Abstract: Root architecture is key in determining how effective plants are at intercepting and absorbing nutrients and water. Previously, the wheat (Triticum aestivum) cultivars Spica and Maringa were shown to have contrasting root morphologies. These cultivars were crossed to generate an F6:1 population of recombinant inbred lines (RILs) which was genotyped using a 90 K single nucleotide polymorphisms (SNP) chip. A total of 227 recombinant inbred lines (RILs) were grown in soil for 21 days in replicated trials under controlled conditions. At harvest, the plants were scored for seven root traits and two shoot traits. An average of 7.5 quantitative trait loci (QTL) were associated with each trait and, for each of these, physical locations of the flanking markers were identified using the Chinese Spring reference genome. We also compiled a list of genes from wheat and other monocotyledons that have previously been associated with root growth and morphology to determine their physical locations on the Chinese Spring reference genome. This allowed us to determine whether the QTL discovered in our study encompassed genes previously associated with root morphology in wheat or other monocotyledons. Furthermore, it allowed us to establish if the QTL were co-located with the QTL identified from previously published studies. The parental lines together with the genetic markers generated here will enable specific root traits to be introgressed into elite wheat lines. Moreover, the comprehensive list of genes associated with root development, and their physical locations, will be a useful resource for researchers investigating the genetics of root morphology in cereals.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.CARRES.2015.05.003
Abstract: Capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii NIPH146, and the following structure of branched pentasaccharide repeating unit was established by sugar analyses along with 1D and 2D NMR spectroscopy: In comparison to most other known capsular polysaccharides of A. baumannii, the CPS studied is neutral and lacks any specific monosaccharide component. The synthesis, assembly and export of this structure could be attributed to genes in a novel capsule biosynthesis gene cluster, designated KL37, which was found in the NIPH146 genome. The CPS of A. baumannii NIPH146 shares the α-d-Galp-(1→6)-β-d-Glcp-(1→3)-d-GalpNAc-(1→ trisaccharide fragment with the CPS units of several A. baumannii strains, including ATCC 17978 and LUH 5537 that carry the KL3 and KL22 gene clusters, respectively. KL37 contains two genes for glycosyltransferases that are related to two glycosyltransferase genes present in both KL3 and KL22, and the encoded proteins could be tentatively assigned to linkages between sugars in the CPS repeat.
Publisher: Elsevier BV
Date: 09-2023
Publisher: SPIE
Date: 21-02-2003
DOI: 10.1117/12.459095
Publisher: Frontiers Media SA
Date: 04-02-2020
Publisher: MDPI AG
Date: 04-03-2023
DOI: 10.3390/AGRICULTURE13030620
Abstract: Safflower (Carthamus tinctorius L.) is a highly adaptable but underutilized oilseed crop capable of growing in marginal environments, with crucial agronomical, commercial, and industrial uses. Considerable research is still needed to develop commercially relevant varieties, requiring effective, high-throughput digital phenotyping to identify key selection traits. In this study, field trials comprising a globally erse collection of 350 safflower genotypes were conducted during 2017–2019. Crop traits assessed included phenology, grain yield, and oil quality, as well as unmanned aerial vehicle (UAV) multispectral data for estimating vegetation indices. Phenotypic traits and crop performance were highly dependent on environmental conditions, especially rainfall. High-performing genotypes had intermediate growth and phenology, with spineless genotypes performing similarly to spiked genotypes. Phenology parameters were significantly correlated to height, with significantly weak interaction with yield traits. The genotypes produced total oil content values ranging from 20.6–41.07%, oleic acid values ranging 7.57–74.5%, and linoleic acid values ranging from 17.0–83.1%. Multispectral data were used to model crop height, NDVI and EVI changes, and crop yield. NDVI data identified the start of flowering and dissected genotypes according to flowering class, growth pattern, and yield estimation. Overall, UAV-multispectral derived data are applicable to phenotyping key agronomical traits in large collections suitable for safflower breeding programs.
Publisher: Public Library of Science (PLoS)
Date: 23-07-2021
DOI: 10.1371/JOURNAL.PONE.0254908
Abstract: Drought is one of the most severe and unpredictable abiotic stresses, occurring at any growth stage and affecting crop yields worldwide. Therefore, it is essential to develop drought tolerant varieties to ensure sustainable crop production in an ever-changing climate. High-throughput digital phenotyping technologies in tandem with robust screening methods enable precise and faster selection of genotypes for breeding. To investigate the use of digital imaging to reliably phenotype for drought tolerance, a genetically erse safflower population was screened under different drought stresses at Agriculture Victoria’s high-throughput, automated phenotyping platform, Plant Phenomics Victoria, Horsham. In the first experiment, four treatments, control (90% field capacity FC), 40% FC at initial branching, 40% FC at flowering and 50% FC at initial branching and flowering, were applied to assess the performance of four safflower genotypes. Based on these results, drought stress using 50% FC at initial branching and flowering stages was chosen to further screen 200 erse safflower genotypes. Measured plant traits and dry biomass showed high correlations with derived digital traits including estimated shoot biomass, convex hull area, caliper length and minimum area rectangle, indicating the viability of using digital traits as proxy measures for plant growth. Estimated shoot biomass showed close association having moderately high correlation with drought indices yield index, stress tolerance index, geometric mean productivity, and mean productivity. Diverse genotypes were classified into four clusters of drought tolerance based on their performance (seed yield and digitally estimated shoot biomass) under stress. Overall, results show that rapid and precise image-based, high-throughput phenotyping in controlled environments can be used to effectively differentiate response to drought stress in a large numbers of safflower genotypes.
Publisher: Springer Science and Business Media LLC
Date: 07-12-2020
DOI: 10.1007/S00122-019-03495-X
Abstract: Resistance QTL to root lesion nematode (Pratylenchus thornei) in wheat (Triticum aestivum), QRlnt.sk-6D and QRlnt.sk-2B, were mapped to intervals of 3.5 cM/1.77 Mbp on chromosome 6D and 1.4 cM/2.19 Mbp on chromosome 2B, respectively. Candidate resistance genes were identified in the QTL regions and molecular markers developed for marker-assisted breeding. Two previously known resistance QTL for root lesion nematode (Pratylenchus thornei) in bread wheat (Triticum aestivum), QRlnt.sk-6D and QRlnt.sk-2B, were fine-mapped using a Sokoll (moderately resistant) by Krichauff (susceptible) doubled haploid (DH) population and six newly developed recombinant inbred line populations. Bulked segregation analysis with the 90K wheat SNP array identified linked SNPs which were subsequently converted to KASP assays for mapping in the DH and RIL populations. On chromosome 6D, 60 KASP and five SSR markers spanned a total genetic distance of 23.7 cM. QRlnt.sk-6D was delimited to a 3.5 cM interval, representing 1.77 Mbp in the bread wheat cv. Chinese Spring reference genome sequence and 2.29 Mbp in the Aegilops tauschii genome sequence. These intervals contained 42 and 43 gene models in the respective annotated genome sequences. On chromosome 2B, 41 KASP and 5 SSR markers produced a map spanning 19.9 cM. QRlnt.sk-2B was delimited to 1.4 cM, corresponding 3.14 Mbp in the durum wheat cv. Svevo reference sequence and 2.19 Mbp in Chinese Spring. The interval in Chinese Spring contained 56 high-confidence gene models. Intervals for both QTL contained genes with similarity to those previously reported to be involved in disease resistance, namely genes for phenylpropanoid biosynthetic pathway-related enzymes, NBS-LRR proteins and protein kinases. The potential roles of these candidate genes in P. thornei resistance are discussed. The KASP markers reported in this study could potentially be used for marker-assisted breeding of P. thornei-resistant wheat cultivars.
Publisher: Informa UK Limited
Date: 2010
Publisher: eLife Sciences Publications, Ltd
Date: 21-12-2018
Publisher: Springer Science and Business Media LLC
Date: 03-2021
Publisher: Elsevier BV
Date: 12-2023
Publisher: Society for Neuroscience
Date: 03-09-2014
DOI: 10.1523/JNEUROSCI.2513-13.2014
Abstract: During brain development, neural progenitor cells proliferate and differentiate into neural precursors. These neural precursors migrate along the radial glial processes and localize at their final destination in the cortex. Numerous reports have revealed that 14-3-3 proteins are involved in many neuronal activities, although their functions in neurogenesis remain unclear. Here, using 14-3-3 ε/ζ double knock-out mice, we found that 14-3-3 proteins are important for proliferation and differentiation of neural progenitor cells in the cortex, resulting in neuronal migration defects and seizures. 14-3-3 deficiency resulted in the increase of δ-catenin and the decrease of β-catenin and αN-catenin. 14-3-3 proteins regulated neuronal differentiation into neurons via direct interactions with phosphorylated δ-catenin to promote F-actin formation through a catenin/Rho GTPase/Limk1/cofilin signaling pathway. Conversely, neuronal migration defects seen in the double knock-out mice were restored by phosphomimic Ndel1 mutants, but not δ-catenin. Our findings provide new evidence that 14-3-3 proteins play important roles in neurogenesis and neuronal migration via the regulation of distinct signaling cascades.
Publisher: Wiley
Date: 03-2020
DOI: 10.1002/CSC2.20113
Abstract: In Australian wheat ( Triticum aestivum L.) production, optimizing wheat phenology is essential for yield potential and to avoid stress, especially around flowering. Breeding could be accelerated by identifying key loci and developing models to predict genotype flowering times under different pedoclimatic scenarios. Here, association genetics for heading date, earliness components (photoperiod sensitivity [PS] vernalization requirement [VR] earliness per se [EPS]) and simulation model (APSIM) phenology parameters from a panel of Australian cultivars and breeding lines identified loci with stable, repeatable effects. Major chromosomal regions with stable effects included the Ppd‐D1 region on chromosome 2D for PS and EPS, one region on 5B for PS, one region on 6B for EPS, and the Vrn‐A1 region on 5A for VR. Regions with stable, smaller effects were detected on 1A and 2D for PS, on 5A and 6B for EPS, and on 1A and 5D for VR. Other regions with stable effects on heading date and earliness components were located on 1A, 2B, 4B, 5B, 6B and 7B (PS and EPS), 2A, 3A and 7A (EPS and VR). Quantitative trait loci (QTL)–based model parameters were used to simulate heading dates across the Australian wheat belt for set of independent genotypes. Comparisons of average observed and predicted heading dates for four main regions of the Australian wheat belt showed good performance in prediction of independent lines from QTL information alone ( r 2 = .61–.83). The model allows testing of putative genotypes under various pedoclimatic scenarios including for adaptation to anticipated climate changes.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.YDBIO.2015.12.001
Abstract: Nedd4 is an E3 ubiquitin ligase that has an essential role in craniofacial development. However, how and when Nedd4 controls skull formation is ill defined. Here we have used a collection of complementary genetic mouse models to dissect the cell-autonomous roles of Nedd4 in the formation of neural crest cell derived cranial bone. Removal of Nedd4 specifically from neural crest cells leads to profound craniofacial defects with marked reduction of cranial bone that was preceded by hypoplasia of bone forming osteoblasts. Removal of Nedd4 after differentiation of neural crest cells into progenitors of chondrocytes and osteoblasts also led to profound deficiency of craniofacial bone in the absence of cartilage defects. Notably, these skull malformations were conserved when Nedd4 was specifically removed from the osteoblast lineage after specification of osteoblast precursors from mesenchymal skeletal progenitors. We further show that absence of Nedd4 in pre-osteoblasts results in decreased cell proliferation and altered osteogenic differentiation. Taken together our data demonstrate a novel cell-autonomous role for Nedd4 in promoting expansion of the osteoblast progenitor pool to control craniofacial development. Nedd4 mutant mice therefore represent a unique mouse model of craniofacial anomalies that provide an ideal resource to explore the cell-intrinsic mechanisms of neural crest cells in craniofacial morphogenesis.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-03-2023
Abstract: Dynamic positioning of endothelial tip and stalk cells, via the interplay between VEGFR2 and NOTCH signaling, is essential for angiogenesis. VEGFR2 activates PI3K, which phosphorylates PI(4,5)P 2 to PI(3,4,5)P 3 , activating AKT however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P 2 hydrolysis by the phosphoinositide-5-phosphatase, INPP5K, contributes to angiogenesis. INPP5K ablation disrupted tip cell specification and impaired embryonic angiogenesis associated with enhanced DLL4/NOTCH signaling. INPP5K degraded a pool of PI(4,5)P 2 generated by PIP5K1C phosphorylation of PI(4)P in endothelial cells. INPP5K ablation increased PI(4,5)P 2 , thereby releasing β-catenin from the plasma membrane, and concurrently increased PI(3,4,5)P 3 -dependent AKT activation, conditions that licensed DLL4 / NOTCH transcription. Suppression of PI(4,5)P 2 in INPP5K -siRNA cells by PIP5K1C -siRNA, restored β-catenin membrane localization and normalized AKT signaling. Pharmacological NOTCH or AKT inhibition in vivo or genetic β-catenin attenuation rescued angiogenesis defects in INPP5K-null mice. Therefore, PI(4,5)P 2 is critical for β-catenin/DLL4/NOTCH signaling, which governs tip cell specification during angiogenesis.
Publisher: Cold Spring Harbor Laboratory
Date: 15-11-2004
DOI: 10.1101/GAD.322904
Abstract: Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2022
DOI: 10.1038/S41419-022-04519-Z
Abstract: Gonadogenesis is the process wherein two morphologically distinct organs, the testis and the ovary, arise from a common precursor. In mammals, maleness is driven by the expression of Sry . SRY subsequently upregulates the related family member Sox9 which is responsible for initiating testis differentiation while repressing factors critical to ovarian development such as FOXL2 and β-catenin. Here, we report a hitherto uncharacterised role for the ubiquitin-protein ligase NEDD4 in this process. XY Nedd4 -deficient mice exhibit complete male-to-female gonadal sex reversal shown by the ectopic upregulation of Foxl2 expression at the time of gonadal sex determination as well as insufficient upregulation of Sox9 . This sex reversal extends to germ cells with ectopic expression of SYCP3 in XY Nedd4-/- germ cells and significantly higher Sycp3 transcripts in XY and XX Nedd4- deficient mice when compared to both XY and XX controls. Further, Nedd4-/ - mice exhibit reduced gonadal precursor cell formation and gonadal size as a result of reduced proliferation within the developing gonad as well as reduced Nr5a1 expression. Together, these results establish an essential role for NEDD4 in XY gonadal sex determination and development and suggest a potential role for NEDD4 in orchestrating these cell fate decisions through the suppression of the female pathway to ensure proper testis differentiation.
Publisher: Frontiers Media SA
Date: 22-12-2021
Abstract: Array-based single nucleotide polymorphism (SNP) genotyping platforms have low genotype error and missing data rates compared to genotyping-by-sequencing technologies. However, design decisions used to create array-based SNP genotyping assays for both research and breeding applications are critical to their success. We describe a novel approach applicable to any animal or plant species for the design of cost-effective imputation-enabled SNP genotyping arrays with broad utility and demonstrate its application through the development of the Illumina Infinium Wheat Barley 40K SNP array Version 1.0. We show that the approach delivers high quality and high resolution data for wheat and barley, including when s les are jointly hybridised. The new array aims to maximally capture haplotypic ersity in globally erse wheat and barley germplasm while minimizing ascertainment bias. Comprising mostly biallelic markers that were designed to be species-specific and single-copy, the array permits highly accurate imputation in erse germplasm to improve the statistical power of genome-wide association studies (GWAS) and genomic selection. The SNP content captures tetraploid wheat (A- and B-genome) and Aegilops tauschii Coss. (D-genome) ersity and delineates synthetic and tetraploid wheat from other wheat, as well as tetraploid species and subgroups. The content includes SNP tagging key trait loci in wheat and barley, as well as direct connections to other genotyping platforms and legacy datasets. The utility of the array is enhanced through the web-based tool, Pretzel ( plantinformatics.io/ ) which enables the content of the array to be visualized and interrogated interactively in the context of numerous genetic and genomic resources to be connected more seamlessly to research and breeding. The array is available for use by the international wheat and barley community.
Publisher: Research Square Platform LLC
Date: 19-09-2023
Publisher: Wiley
Date: 24-10-2015
DOI: 10.1002/DVG.22905
Abstract: We have established a novel Cre mouse line, using genomic elements encompassing the Nrp2 locus, present within a bacterial artificial chromosome clone. By crossing this Cre driver line to R26R LacZ reporter mice, we have documented the temporal expression and lineage traced tissues in which Cre is expressed. Nrp2-Cre drives expression in primitive blood cells arising from the yolk sac, venous and lymphatic endothelial cells, peripheral sensory ganglia, and the lung bud. This mouse line will provide a new tool to researchers wishing to study the development of various tissues and organs in which this Cre driver is expressed, as well as allow tissue-specific knockout of genes of interest to study protein function. This work also presents the first evidence for expression of Nrp2 protein in a mesodermal progenitor with restricted hematopoietic potential, which will significantly advance the study of primitive erythropoiesis. genesis 53:709-717, 2015. © 2015 Wiley Periodicals, Inc.
Publisher: Springer New York
Date: 2008
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.DEVCEL.2008.09.005
Abstract: Energy generation by mitochondrial respiration is an absolute requirement for cardiac function. Here, we used a heart-specific conditional knockout approach to inactivate the X-linked gene encoding Holocytochrome c synthase (Hccs), an enzyme responsible for activation of respiratory cytochromes c and c1. Heterozygous knockout female mice were thus mosaic for Hccs function due to random X chromosome inactivation. In contrast to midgestational lethality of Hccs knockout males, heterozygous females appeared normal after birth. Analyses of heterozygous embryos revealed the expected 50:50 ratio of Hccs deficient to normal cardiac cells at midgestation however, diseased tissue contributed progressively less over time and by birth represented only 10% of cardiac tissue volume. This change is accounted for by increased proliferation of remaining healthy cardiac cells resulting in a fully functional heart. These data reveal an impressive regenerative capacity of the fetal heart that can compensate for an effective loss of 50% of cardiac tissue.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2022
DOI: 10.1038/S41467-022-29660-3
Abstract: The ubiquitin ligase NEDD4 promotes neural crest cell (NCC) survival and stem-cell like properties to regulate craniofacial and peripheral nervous system development. However, how ubiquitination and NEDD4 control NCC development remains unknown. Here we combine quantitative analysis of the proteome, transcriptome and ubiquitinome to identify key developmental signalling pathways that are regulated by NEDD4. We report 276 NEDD4 targets in NCCs and show that loss of NEDD4 leads to a pronounced global reduction in specific ubiquitin lysine linkages. We further show that NEDD4 contributes to the regulation of the NCC actin cytoskeleton by controlling ubiquitination and turnover of Profilin 1 to modulate filamentous actin polymerization. Taken together, our data provide insights into how NEDD4-mediated ubiquitination coordinates key regulatory processes during NCC development.
Publisher: eLife Sciences Publications, Ltd
Date: 19-02-2019
DOI: 10.7554/ELIFE.40093
Abstract: The vertebrate eye originates from the eye field, a domain of cells specified by a small number of transcription factors. In this study, we show that Tcf7l1a is one such transcription factor that acts cell-autonomously to specify the eye field in zebrafish. Despite the much-reduced eye field in tcf7l1a mutants, these fish develop normal eyes revealing a striking ability of the eye to recover from a severe early phenotype. This robustness is not mediated through genetic compensation at neural plate stage instead, the smaller optic vesicle of tcf7l1a mutants shows delayed neurogenesis and continues to grow until it achieves approximately normal size. Although the developing eye is robust to the lack of Tcf7l1a function, it is sensitised to the effects of additional mutations. In support of this, a forward genetic screen identified mutations in hesx1, cct5 and gdf6a, which give synthetically enhanced eye specification or growth phenotypes when in combination with the tcf7l1a mutation.
Publisher: Wiley
Date: 22-06-2021
DOI: 10.1002/CSC2.20460
Abstract: Genotype × environment interaction (GEI) is one of the key factors affecting breeding value estimation accuracy for agronomic traits in plant breeding. Measures of GEI include fitting prediction models with various kernels to capture the variance resulting from GEI, and characterizing trials into megaenvironment (ME) clusters within which breeding values can be estimated to remove the main GEI effects. However, many of the current approaches require observations of common genotypes across all trials, which is unavailable in most breeding programs. Our study introduces two methods that can be implemented on unbalanced data to categorize trials into clusters, where both need a correlation matrix between trials: one estimated via a factor analytic (FA) model and another estimated via weather variables. The methods were tested using empirical barley ( Hordeum vulgare L.) yield data in a commercial breeding program from 102 trials over 5 yr spread across multiple locations in Australia. Leave‐one‐year‐out cross‐validation achieved comparable predictive accuracies using either trials or clusters as the observed variable in GEI FA models (max. 0.45), which was higher than the accuracy achieved using the non‐GEI model (0.37). In the random cross‐validations, accuracies achieved within clusters (0.42–0.64) were mostly comparable with those achieved in the full population (0.62). In the within‐cluster validations, higher predictive accuracies were achieved when the training population was from the same cluster (mean 0.22) than outside of the cluster (mean 0.16). Our proposed methods of characterizing multienvironment trials into clusters provides a novel way to define training populations by reducing the variance resulting from GEI and could be implemented in any plant breeding program.
Publisher: MDPI AG
Date: 10-01-2022
DOI: 10.3390/IJMS23020713
Abstract: Bread wheat is the most widely cultivated crop worldwide, used in the production of food products and a feed source for animals. Selection tools that can be applied early in the breeding cycle are needed to accelerate genetic gain for increased wheat production while maintaining or improving grain quality if demand from human population growth is to be fulfilled. Proteomics screening assays of wheat flour can assist breeders to select the best performing breeding lines and discard the worst lines. In this study, we optimised a robust LC–MS shotgun quantitative proteomics method to screen thousands of wheat genotypes. Using 6 cultivars and 4 replicates, we tested 3 resuspension ratios (50, 25, and 17 µL/mg), 2 extraction buffers (with urea or guanidine-hydrochloride), 3 sets of proteases (chymotrypsin, Glu-C, and trypsin/Lys-C), and multiple LC settings. Protein identifications by LC–MS/MS were used to select the best parameters. A total 8738 wheat proteins were identified. The best method was validated on an independent set of 96 cultivars and peptides quantities were normalised using s le weights, an internal standard, and quality controls. Data mining tools found particularly useful to explore the flour proteome are presented (UniProt Retrieve/ID mapping tool, KEGG, AgriGO, REVIGO, and Pathway Tools).
Publisher: Proceedings of the National Academy of Sciences
Date: 28-04-2015
Abstract: Craniofacial development is a complex morphogenic event that relies on highly orchestrated interactions between multiple cell types. Since the first description of Meckel’s cartilage in the lower jaw more than 180 years ago, we have come to realize that expansion of this specialized structure underpins correct mandible development. Here we demonstrate that an intricate association between neural crest cells and blood vessels plays an important role in promoting chondrocyte proliferation and expansion of Meckel’s cartilage as a prerequisite of correct mandibular morphogenesis. These findings provide direct insight into the origins and potential treatments of highly prevalent disorders affecting the mandible.
Publisher: Frontiers Media SA
Date: 21-12-2020
Abstract: Representative, broad and erse collections are a primary resource to dissect genetic ersity and meet pre-breeding and breeding goals through the identification of beneficial alleles for target traits. From 2,500 tetraploid wheat accessions obtained through an international collaborative effort, a Global Durum wheat Panel (GDP) of 1,011 genotypes was assembled that captured 94–97% of the original ersity. The GDP consists of a wide representation of Triticum turgidum ssp. durum modern germplasm and landraces, along with a selection of emmer and primitive tetraploid wheats to maximize ersity. GDP accessions were genotyped using the wheat iSelect 90K SNP array. Among modern durum accessions, breeding programs from Italy, France and Central Asia provided the highest level of genetic ersity, with only a moderate decrease in genetic ersity observed across nearly 50 years of breeding (1970–2018). Further, the breeding programs from Europe had the largest sets of unique alleles. LD was lower in the landraces (0.4 Mbp) than in modern germplasm (1.8 Mbp) at r 2 = 0.5. ADMIXTURE analysis of modern germplasm defined a minimum of 13 distinct genetic clusters ( k ), which could be traced to the breeding program of origin. Chromosome regions putatively subjected to strong selection pressure were identified from fixation index ( F st ) and ersity reduction index ( DRI ) metrics in pairwise comparisons among decades of release and breeding programs. Clusters of putative selection sweeps (PSW) were identified as co-localized with major loci controlling phenology ( Ppd and Vrn ), plant height ( Rht ) and quality (gliadins and glutenins), underlining the role of the corresponding genes as driving elements in modern breeding. Public seed availability and deep genetic characterization of the GDP make this collection a unique and ideal resource to identify and map useful genetic ersity at loci of interest to any breeding program.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.BIOCEL.2013.02.014
Abstract: Neural crest cells are a transient population of stem cells that give rise to a erse range of cell types during embryonic development. Through gain-of-function and loss-of-function studies in several model organisms many key signalling pathways and cell-type specific transcription factors essential for neural crest cell development have been identified. However, the role of post-translational regulation remains largely unexplored. Here we review this cell type with a foray into the known and potential roles of the ubiquitination pathway in key signalling events during neural crest cell development.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.YDBIO.2013.09.024
Abstract: The integration of multiple morphogenic signalling pathways and transcription factor networks is essential to mediate neural crest (NC) cell induction, delamination, survival, stem-cell properties, fate choice and differentiation. Although the transcriptional control of NC development is well documented in mammals, the role of post-transcriptional modifications, and in particular ubiquitination, has not been explored. Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-) embryos identified profound deficiency of cranial NC cells in the absence of structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC cells and was found to positively regulate expression of the NC transcription factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a subset of cranial NC cells undergo apoptosis. In accordance with a lack of cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia, NC derived bone and malformation of the craniofacial skeleton. Our analyses therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC signalling pathways and transcription factor networks.
Publisher: IOP Publishing
Date: 09-02-2004
Publisher: Wiley
Date: 10-01-2015
DOI: 10.1111/DGD.12189
Abstract: Neural crest cells (NCCs) are highly migratory progenitor cells that give rise to a vast array of differentiated cell types. One of their key derivatives is the autonomic nervous system (ANS) that is comprised in part from chromaffin cells of the adrenal medulla and organ of Zuckerkandl, the sympathetic chain and additional prevertebral ganglia such as the celiac ganglia, suprarenal ganglia and mesenteric ganglia. In this review we discuss recent advances toward our understanding of how the NCC precursors of the ANS migrate to their target regions, how they are instructed to differentiate into the correct cell types, and the morphogenetic signals controlling their development. Many of these processes remain enigmatic to developmental biologists worldwide. Taking advantage of lineage tracing mouse models one of our own aims is to address the morphogenetic events underpinning the formation of the ANS and to identify the molecular mechanisms that help to segregate a mixed population of NCCs into pathways specific for the sympathetic ganglia, sensory ganglia or adrenal medulla.
Publisher: Frontiers Media SA
Date: 28-05-2020
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.PBB.2015.09.006
Abstract: Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain s les were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippoc al laminar defects or decreased dendritic spine density observed in 14-3-3ζ KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14-3-3ζ molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug.
Publisher: The Company of Biologists
Date: 15-09-2011
DOI: 10.1242/DEV.062695
Abstract: During tissue morphogenesis and differentiation, cells must self-renew while contemporaneously generating daughters that contribute to the growing tissue. How tissues achieve this precise balance between proliferation and differentiation is, in most instances, poorly understood. This is in part due to the difficulties in dissociating the mechanisms that underlie tissue patterning from those that regulate proliferation. In the migrating posterior lateral line primordium (PLLP), proliferation is predominantly localised to the leading zone. As cells emerge from this zone, they periodically organise into rosettes that subsequently dissociate from the primordium and differentiate as neuromasts. Despite this reiterative loss of cells, the primordium maintains its size through regenerative cell proliferation until it reaches the tail. In this study, we identify a null mutation in the Wnt-pathway transcription factor Lef1 and show that its activity is required to maintain proliferation in the progenitor pool of cells that sustains the PLLP as it undergoes migration, morphogenesis and differentiation. In absence of Lef1, the leading zone becomes depleted of cells during its migration leading to the collapse of the primordium into a couple of terminal neuromasts. We show that this behaviour resembles the process by which the PLLP normally ends its migration, suggesting that suppression of Wnt signalling is required for termination of neuromast production in the tail. Our data support a model in which Lef1 sustains proliferation of leading zone progenitors, maintaining the primordium size and defining neuromast deposition rate.
Publisher: MDPI AG
Date: 19-06-2023
Abstract: Soil salinity can impose substantial stress on plant growth and cause significant yield losses. Crop varieties tolerant to salinity stress are needed to sustain yields in saline soils. This requires effective genotyping and phenotyping of germplasm pools to identify novel genes and QTL conferring salt tolerance that can be utilised in crop breeding schemes. We investigated a globally erse collection of 580 wheat accessions for their growth response to salinity using automated digital phenotyping performed under controlled environmental conditions. The results show that digitally collected plant traits, including digital shoot growth rate and digital senescence rate, can be used as proxy traits for selecting salinity-tolerant accessions. A haplotype-based genome-wide association study was conducted using 58,502 linkage disequilibrium-based haplotype blocks derived from 883,300 genome-wide SNPs and identified 95 QTL for salinity tolerance component traits, of which 54 were novel and 41 overlapped with previously reported QTL. Gene ontology analysis identified a suite of candidate genes for salinity tolerance, some of which are already known to play a role in stress tolerance in other plant species. This study identified wheat accessions that utilise different tolerance mechanisms and which can be used in future studies to investigate the genetic and genic basis of salinity tolerance. Our results suggest salinity tolerance has not arisen from or been bred into accessions from specific regions or groups. Rather, they suggest salinity tolerance is widespread, with small-effect genetic variants contributing to different levels of tolerance in erse, locally adapted germplasm.
Publisher: MDPI AG
Date: 05-10-2023
Publisher: Wiley
Date: 20-07-2007
Publisher: Springer Science and Business Media LLC
Date: 03-12-2013
DOI: 10.1038/TP.2013.99
Publisher: Springer Science and Business Media LLC
Date: 12-07-2021
Publisher: Elsevier BV
Date: 12-2008
Publisher: MDPI AG
Date: 17-08-2023
DOI: 10.3390/BIOMEDICINES11082290
Abstract: The aim of the present study was to gain a better understanding of the role of brain-derived neurotrophic factor (BDNF) and dopamine D3 receptors in the effects of chronic meth hetamine (METH) on prepulse inhibition (PPI), an endophenotype of psychosis. We compared the effect of a three-week adolescent METH treatment protocol on the regulation of PPI in wildtype mice, BDNF heterozygous mice (HET), D3 receptor knockout mice (D3KO), and double-mutant mice (DM) with both BDNF heterozygosity and D3 receptor knockout. Chronic METH induced disruption of PPI regulation in male mice with BDNF haploinsufficiency (HET and DM), independent of D3 receptor knockout. Specifically, these mice showed reduced baseline PPI, as well as attenuated disruption of PPI induced by acute treatment with the dopamine receptor agonist, apomorphine (APO), or the glutamate NMDA receptor antagonist, MK-801. In contrast, there were no effects of BDNF heterozygosity or D3 knockout on PPI regulation in female mice. Chronic METH pretreatment induced the expected locomotor hyperactivity sensitisation, where female HET and DM mice also showed endogenous sensitisation. Differential sex-specific effects of genotype and METH pretreatment were observed on dopamine receptor and dopamine transporter gene expression in the striatum and frontal cortex. Taken together, these results show a significant involvement of BDNF in the long-term effects of METH on PPI, particularly in male mice, but these effects appear independent of D3 receptors. The role of this receptor in psychosis endophenotypes therefore remains unclear.
Start Date: 2022
End Date: 2025
Funder: Research and Education Foundation of the American Head and Neck Society
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: Australian Research Council
View Funded ActivityStart Date: 2021
End Date: 2022
Funder: Australian Research Council
View Funded ActivityStart Date: 2019
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2021
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 2015
Funder: Australian Research Council
View Funded Activity