ORCID Profile
0000-0003-4461-4197
Current Organisation
University of Tasmania
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Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1016/S1567-133X(03)00028-0
Abstract: Tumor necrosis factor receptor-associated factors (TRAFs) belong to a family of intracellular adaptor proteins that mediate signaling downstream of various cell surface receptors. We carried out comparative in situ hybridization analysis of five Traf genes Traf1, Traf2, Traf3, Traf4 and Traf6 during murine odontogenesis from the formation of the epithelial thickening to the early bell stage. Traf2, Traf3 and Traf6 showed weak expression in the thickened epithelium. Expression of Traf1, Traf2 and Traf6 were observed in the outer edges of the bud epithelium whereas Traf3 was strongly expressed at the tip of the bud epithelium. Expression of Traf1, Traf4 and Traf6 were detected in the dental papilla mesenchyme. Traf2 showed restricted expression in the internal enamel epithelium of the bell stage while expression of Traf1, Traf3, Traf4 and Traf6 were observed in both the internal and the external enamel epithelium. During early odontogenesis, all five genes show dynamic spatiotemporal expression patterns.
Publisher: Wiley
Date: 11-06-2023
DOI: 10.1002/GLIA.24208
Publisher: SAGE Publications
Date: 03-2004
DOI: 10.1177/154405910408300311
Abstract: Osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.
Publisher: Cold Spring Harbor Laboratory
Date: 10-2023
Publisher: Wiley
Date: 22-11-2023
DOI: 10.1002/JNR.25146
Abstract: Stroke therapy has largely focused on preventing damage and encouraging repair outside the ischemic core, as the core is considered irreparable. Recently, several studies have suggested endogenous responses within the core are important for limiting the spread of damage and enhancing recovery, but the role of blood flow and capillary pericytes in this process is unknown. Using the Rose Bengal photothrombotic model of stroke, we illustrate blood vessels are present in the ischemic core and peri-lesional regions 2 weeks post stroke in male mice. A FITC-albumin gel cast of the vasculature revealed perfusion of these vessels, suggesting cerebral blood flow (CBF) may be partially present, without vascular leakage. The length of these vessels is significantly reduced compared to uninjured regions, but the average width is greater, suggesting they are either larger vessels that survived the initial injury, smaller vessels that have expanded in size (i.e., arteriogenesis), or that neovascularization begins with larger vessels. Concurrently, we observed an increase in platelet-derived growth factor receptor beta (PDGFRβ, a marker of pericytes) expression within the ischemic core in two distinct patterns, one which resembles pericyte-derived fibrotic scarring at the edge of the core, and one which is vessel associated and may represent blood vessel recovery. We find little evidence for iding cells on these intralesional blood vessels 2 weeks post stroke. Our study provides evidence flow is present in PDGFRβ-positive vessels in the ischemic core 2 weeks post stroke. We hypothesize intralesional CBF is important for limiting injury and for encouraging endogenous repair following cerebral ischemia.
Publisher: Elsevier BV
Date: 02-2000
DOI: 10.1016/S0006-8993(99)02455-5
Abstract: Ensheathing cells were isolated from neonatal rat olfactory bulbs and cultured in the presence of glial growth factor 2 (GGF2). Proliferation assay showed that at concentrations of up to 60 ng/ml GGF2, ensheathing cells underwent a modest increase in proliferation rate. This stimulation was not maintained at high doses of GGF2 at 100 ng/ml or more. Chemotaxis chambers and scanning electron microscopy were used to determine whether GGF2 was a chemoattractant for ensheathing cells. Although the results showed no chemotactic response to GGF2, ensheathing cells demonstrated structural changes when cultured in the presence of 20 ng/ml GGF2. Ultrastructural observations revealed that GGF2 promoted increased deposition of extracellular matrix on the cell membrane, more cytoskeletal elements in the processes and as a possible consequence, contributed to a more rigid support. Ensheathing cells cultured in the absence of GGF2 often extended thinner and curved processes. Reverse transcription-polymerase chain reaction confirmed the presence of GGF2 transcripts in ensheathing cells, suggesting that ensheathing cells themselves are a source of GGF2.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000450919
Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide, and there is currently no treatment that can halt the progression of the disease. Over the last decade there has been increasing interest in the idea that epithelial-mesenchymal transition (EMT) may be active in COPD. Here we review the evidence for EMT in COPD as well as the current progress being made on understanding the drivers and mechanisms involved. Finally, we discuss the potential benefits that understanding EMT may bring to the field of chronic respiratory disease.
Publisher: Frontiers Media SA
Date: 28-06-2019
Publisher: Medknow
Date: 2020
Publisher: Elsevier BV
Date: 03-2002
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.ARCHORALBIO.2004.11.019
Abstract: Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder affecting organs of ectodermal origin including teeth, hair and sweat glands. Defects in Ectodysplasin (tabby), Edar (downless) and Edar associated death domain (Edaradd) (crinkled) cause HED in both humans and mice. Ectodysplasin is a tumour necrosis factor (TNF) superfamily member whose downstream signalling is transduced by the inhibitor of kappaB kinase (IKK) complex and inhibitors of kappaB (IkappaB) to activate the transcription factor NFkappaB. NFkappaB signalling is involved in a wide range of cellular processes and at each stage the different family members must be tightly regulated for each function. Recent data have demonstrated the importance of this signalling pathway in odontogenesis, particularly in the formation of cusps. Here we review recent advances in our understanding of Ectodysplasin/NFkappaB signalling in tooth development and in particular the central role of the IKK complex.
Publisher: Society for Neuroscience
Date: 12-10-2021
DOI: 10.1523/ENEURO.0177-21.2021
Abstract: Whole slide scanning technology has enabled the generation of high-resolution images from complete tissue sections. However, commonly used analysis software is often unable to handle the large data files produced. Here, we present a method using the open-source software QuPath to detect, classify and quantify fluorescently-labeled cells (microglia and pericytes) in whole coronal brain tissue sections. Whole-brain sections from both male and female NG2DsRed x CX 3 CR1 +/GFP mice were analyzed. Small regions of interest were selected and manual counts were compared with counts generated from an automated approach, across a range of detection parameters. The optimal parameters for detecting cells and classifying them as microglia or pericytes in each brain region were determined and applied to annotations corresponding to the entire somatosensory and motor cortices, hippoc us, thalamus, and hypothalamus in each section. 3.74% of all detected cells were classified as pericytes however, this proportion was significantly higher in the thalamus (6.20%) than in other regions. In contrast, microglia (4.51% of total cells) were more abundant in the cortex (5.54%). No differences were detected between male and female mice. In conclusion, QuPath offers a user-friendly solution to whole-slide image analysis which could lead to important new discoveries in both health and disease.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.BRAINRESBULL.2019.12.005
Abstract: Neuroprotection for stroke has shown great promise but has had little translational success. Developing drugs for humans logically requires human tissue evaluation. Human embryonic stem cell (hESC)-derived neuronal cultures at different developmental stages were subject to oxygen glucose deprivation (OGD) to determine how developing maturity altered response to ischemic injury. H9 hESCs were induced by Noggin to generate neural progenitors (NPs) and highly arbourised structurally complex neurons. They were both subjected to OGD or OGD with reoxygenation (OGD-R) for 1-6 h.Outcome was assessed by measures of cell death, survival and morphology. NPs did not die after OGD but experienced progressive loss of metabolic activity. Highly arbourised neurons showed minimal cell death initially but 44 % and 78 % died after 4 and 6 h OGD. Metabolic dysfunction was greater in these more mature neurons (∼70 %) than in NPs and evident after 1 h OGD, before detection of neuronal death at 4 h. OGD-R salvaged metabolic activity but not cell death in mature neurons. In NPs there was little metabolic salvage and cell death was induced (50 % and 65 % at 4 and 6 h OGD-R, respectively). Highly arbourised neurons are more sensitive to ischaemic injury than NPs which did however develop marked vulnerability to prolonged injury with reoxygenation. These observations imply that therapeutic potential may be highly dependent of the developmental state of the neurons we aim to protect.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Wiley
Date: 30-03-2023
DOI: 10.1002/GLIA.24371
Abstract: Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the blood–brain‐barrier (BBB). We explored the relationship between microglia and pericytes, a vessel‐resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte‐associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed × CX 3 CR1 +/GFP mice, and in the human frontal cortex. Using in vivo two‐photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX 3 CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.
Publisher: Wiley
Date: 25-11-2003
DOI: 10.1002/DVDY.10400
Abstract: Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.
Publisher: Cold Spring Harbor Laboratory
Date: 11-08-2022
DOI: 10.1101/2022.08.08.503250
Abstract: Cerebral blood flow is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer’s disease (AD). Subpopulations of microglia have well-characterised associations with the vasculature in the central nervous system but the precise relationship between microglia and cells which exist on the vasculature is not yet clear. In this study we explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the regulation of cerebral blood flow and maintenance of the blood brain barrier. Using fixed tissue sections and in vivo live imaging, we discovered a subset of microglia that closely associated with pericytes, termed PE ricyte-associated M icroglia (PEM). PEM are present throughout all regions of the brain and spinal cord in NG2DsRed x CX 3 CR1 +/GFP mice, and in the human frontal cortex. They reside adjacent to pericytes at all levels of the capillary tree and can maintain their position for at least 28 days. PEM associate with pericytes lacking astroglial endfeet coverage but are segregated from pericytes by capillary basement membranes and capillary vessel width is similarly increased beneath pericytes with or without an associated PEM. Deletion of the microglia fractalkine receptor (CX 3 CR1) did not disrupt the association between pericytes and PEM, suggesting the association is not reliant on fractalkine signalling. Finally, we found that the proportion of microglia that are capillary-associated and PEM declines in the superior frontal gyrus (SFG) in AD, which is exacerbated by the APOE ε3/ε4 genotype. In summary, we identify and characterise a subpopulation of microglia that specifically associate with pericytes and find this population is reduced in the SFG in AD. This reduction may be a novel mechanism contributing to vascular dysfunction in diseases such as AD.
No related grants have been discovered for Jo-Maree Courtney.