Bone. 2020 Dec 2020
Publish at 18.11.2019
Presentation
Genetic disorders of the skeletal system may affect bone and/or cartilage formation from early embryo-fetal development up to childhood. Skeletal development is a temporally-regulated non-linear process orchestrated by a complex genetic network that proceeds via two distinct ossification mechanisms, namely membranous and endochondral. An impairment of this process is responsible for a group of rare and often severe disorders: the osteochondrodysplasia.
Our research aims to contribute to the understanding of the ossification process by:
- Identifying the molecular basis of osteochondrodyplasias, studying large cohort of patients clinically well characterized through the reference center for skeletal dysplasia.
- Developing novel therapeutic approaches in bone fragility disorders using human osteoblasts and mouse models.
- Deciphering proteoglycan synthesis impairment, in chondrodysplasia with multiple dislocations, using cellular and mouse models.
- Understanding the link between of ADAMTS(L) proteins and the related microfibrillar network, TGFb signaling, and ossification processes, using cellular and mouse models with short and tall stature phenotypes.
- Elucidating the molecular and cellular mechanisms involved in craniofacial development using Fgfr3 zebrafish lines.
- Providing an in-depth understanding of FGFR3 signalling in axial skeleton formation.
- Evaluating the relationships between FGFR3 gain-of-function mutations and signalling pathways involved in primary cilia and in cartilage and bone lineage cells.
- Conducting pre-clinical studies to test and identify drugs able to correct long bone growth plate, craniofacial and spine anomalies in achondroplasia and hypochondroplasia mouse models.
Team
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Laurence Legeai-Mallet
chef d'équipe
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Valérie Cormier-Daire
chef d'équipe
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Emilie Dambroise
Postdoctoral fellow
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Maud De Dieuleveult
Chargée de Recherche Inserm
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Céline Huber
Research Engineer
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Corinne Collet
PU PH
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Amélie de la Séglière
Ingénieur d'étude
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Alice Costantini
Post-Doctorante
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Matthias Guillo
Ingénieur d'étude
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Miriam Villegas Villarroel
Doctorante
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Nabil Kaci
Study engineer
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Neha Mohanpuria
Doctorante
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Yvan Marc
Ingénieur d'étude
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Pauline Marzin
Doctorante
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Anne Morice
Doctorantes en sciences médicales
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Rachel Pereur
Doctorante
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Camille Viaut
Post Doctorante
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Alexia Kany
Master2
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Clara Lemoine
Ingénieur d'étude
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Maelle Charpie
CCA AHU
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Stéphanie Panier
PU PH
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Fabien Maury
Doctorant
Resources & publications
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Ther Adv Endocrinol Metab. 2020
New perspectives on the treatment of skeletal dysplasia.
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J. Bone Miner. Res. 2020
Fgfr3 Is a Positive Regulator of Osteoblast Expansion and Differentiation Dur...
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J. Bone Miner. Res. 2020
Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe...
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Eur J Hum Genet 2018
Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodyso...
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Neurochirurgie 2019
Animal models of craniosynostosis.
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Hum. Mol. Genet. 2018
Constitutively-active FGFR3 disrupts primary cilium length and IFT20 traffick...
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Dev. Dyn. 2017
Achondroplasia: Development, pathogenesis, and therapy.
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Am J Hum Genet 2014
XYLT1 mutations in Desbuquois dysplasia type 2.
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Am J Hum Genet 2009
Identification of CANT1 mutations in Desbuquois dysplasia.
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Am J Hum Genet 2013
WDR34 mutations that cause short-rib polydactyly syndrome type III/severe asp...