ORCID Profile
0000-0001-5189-1227
Current Organisations
Brigham and Women's Hospital
,
Harvard Medical School
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Publisher: The Company of Biologists
Date: 15-03-2018
DOI: 10.1242/DEV.157339
Abstract: Body skeletal muscles derive from the paraxial mesoderm, which forms in the posterior region of the embryo. Using microarrays, we characterize novel mouse presomitic mesoderm (PSM) markers and show that, unlike the abrupt transcriptome reorganization of the PSM, neural tube differentiation is accompanied by progressive transcriptome changes. The early paraxial mesoderm differentiation stages can be efficiently recapitulated
Publisher: Wiley
Date: 23-12-2008
DOI: 10.1111/J.1749-6632.2008.03452.X
Abstract: Vertebral malformations contribute substantially to the pathophysiology of kyphosis and scoliosis, common health problems associated with back and neck pain, disability, cosmetic disfigurement, and functional distress. This review explores (1) recent advances in the understanding of the molecular embryology underlying vertebral development and relevance to elucidation of etiologies of several known human vertebral malformation syndromes (2) outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformation and (3) complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and nonsyndromic congenital vertebral malformation. Discussion includes exploration of the importance of establishing improved classification systems for vertebral malformation, future directions in molecular and genetic research approaches to vertebral malformation, and translational value of research efforts to clinical management and genetic counseling of affected in iduals and their families.
Publisher: Informa UK Limited
Date: 10-2008
DOI: 10.1517/17530059.2.10.1107
Abstract: Vertebral malformations contribute substantially to the pathophysiology of kyphosis and scoliosis, common health problems associated with back and neck pain, disability, cosmetic disfigurement and functional distress. To provide an overview of the current understanding of vertebral malformations, at both the clinical level and the molecular level, and factors that contribute to their occurrence. The literature related to the following was reviewed: recent advances in the understanding of the molecular embryology underlying vertebral development and relevance to elucidation of etiologies of several known human vertebral malformation syndromes outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformations and complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and non-syndromic congenital vertebral malformations. Expert opinions extend to discussion of the importance of establishing improved classification systems for vertebral malformation, future directions in molecular and genetic research approaches to vertebral malformation and translational value of research efforts to clinical management and genetic counseling of affected in iduals and their families.
Publisher: Proceedings of the National Academy of Sciences
Date: 17-08-2015
Abstract: The vertebral column provides essential structural and protective functions. The total number of vertebral elements and their specific morphologies are remarkably reproducible within a given species, yet can be tailored to the requirements of separate vertebrate species. Major genetic determinants driving formation of the vertebral column are known, but how they are regulated to achieve a highly reproducible structure remains to be fully elucidated. In this report, we show that the miR-196 family of microRNAs are essential in defining correct vertebral number and vertebral identity in mouse. We reveal the molecular landscape controlled, either directly or indirectly, by miR-196 activity, to demonstrate that miR-196 impacts many key developmental signalling pathways and reinforces a timely trunk-to-tail Hox code transition.
Publisher: Wiley
Date: 11-05-2007
DOI: 10.1002/DVDY.21182
Abstract: Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause erse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.
Publisher: Cold Spring Harbor Laboratory
Date: 29-10-2020
DOI: 10.1101/2020.10.29.360826
Abstract: Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro . Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.
Publisher: Hindawi Limited
Date: 2005
DOI: 10.1002/CFG.485
Publisher: BMJ
Date: 10-04-2014
DOI: 10.1136/JMEDGENET-2013-102067
Abstract: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Here, we report the first ICSG study, a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts. We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22×10-43 for rs11190870, and P=2.94×10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ∼25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-06-2003
Publisher: Cold Spring Harbor Laboratory
Date: 18-01-2201
DOI: 10.1101/101451
Abstract: Mammalian embryos transiently exhibit aerobic glycolysis (Warburg effect), a metabolic adaptation also observed in cancer cells. The role of this particular type of metabolism during vertebrate organogenesis is currently unknown. Here, we provide evidence for spatio-temporal regulation of aerobic glycolysis in the posterior region of mouse and chicken embryos. We show that a posterior glycolytic gradient is established in response to graded transcription of glycolytic enzymes downstream of FGF signaling. We demonstrate that glycolysis controls posterior elongation of the embryonic axis by regulating cell motility in the presomitic mesoderm and by controlling specification of the paraxial mesoderm fate in the tail bud. Our results suggest that Warburg metabolism in the tail bud coordinates Wnt and FGF signaling to promote elongation of the embryonic axis.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2014
DOI: 10.1038/NATURE13819
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.DEVCEL.2006.02.011
Abstract: The segmented body plan of vertebrate embryos arises through segmentation of the paraxial mesoderm to form somites. The tight temporal and spatial control underlying this process of somitogenesis is regulated by the segmentation clock and the FGF signaling wavefront. Here, we report the cyclic mRNA expression of Snail 1 and Snail 2 in the mouse and chick presomitic mesoderm (PSM), respectively. Whereas Snail genes' oscillations are independent of NOTCH signaling, we show that they require WNT and FGF signaling. Overexpressing Snail 2 in the chick embryo prevents cyclic Lfng and Meso 1 expression in the PSM and disrupts somite formation. Moreover, cells mis-expressing Snail 2 fail to express Paraxis, remain mesenchymal, and are thereby inhibited from undergoing the epithelialization event that culminates in the formation of the epithelial somite. Thus, Snail genes define a class of cyclic genes that coordinate segmentation and PSM morphogenesis.
Location: United States of America
Location: France
No related grants have been discovered for Olivier Pourquie.