Fgfr3 Is a Positive Regulator of Osteoblast Expansion and Differentiation During Zebrafish Skull Vault Development.

Autor: Dambroise E; Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Ktorza I; Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Brombin A; MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Abdessalem G; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Edouard J; UMS AMAGEN, CNRS, INRA, Université Paris-Saclay, Gif-sur-Yvette, France.; Institute for Integrative Biology of the Cell (I2BC)-CNRS, Gif-sur-Yvette, France., Luka M; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Fiedler I; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Binder O; Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Pelle O; Flow Cytometry Core Facility, Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS3633, Paris, France., Patton EE; MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Busse B; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Menager M; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France., Sohm F; UMS AMAGEN, CNRS, INRA, Université Paris-Saclay, Gif-sur-Yvette, France.; Institute for Integrative Biology of the Cell (I2BC)-CNRS, Gif-sur-Yvette, France.; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Flow Cytometry Core Facility, Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS3633, Paris, France.; Functional Genomics Institute of Lyon, University of Lyon, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon, France., Legeai-Mallet L; Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France.
Jazyk: angličtina
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2020 Sep; Vol. 35 (9), pp. 1782-1797. Date of Electronic Publication: 2020 May 26.
DOI: 10.1002/jbmr.4042
Abstrakt: Gain or loss-of-function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects highlighting the protein's role in membranous ossification. Zebrafish express high levels of fgfr3 during skull development; in order to study FGFR3's role in cranial vault development, we generated the first fgfr3 loss-of-function zebrafish (fgfr3 lof/lof ). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivo imaging and single-cell RNA sequencing of the osteoblast lineage) of zebrafish fgfr3 lof/lof revealed a delay in osteoblast expansion and differentiation, together with changes in the extracellular matrix. These findings demonstrate that fgfr3 is a positive regulator of osteogenesis. We conclude that changes in the extracellular matrix within growing bone might impair cell-cell communication, mineralization, and new osteoblast recruitment. © 2020 American Society for Bone and Mineral Research.
(© 2020 American Society for Bone and Mineral Research.)
Databáze: MEDLINE
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