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

Abstract : 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. (c) 2020 American Society for Bone and Mineral Research.
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https://hal.inrae.fr/hal-03257993
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Submitted on : Friday, June 11, 2021 - 11:32:51 AM
Last modification on : Friday, September 17, 2021 - 4:43:17 PM

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Emilie Dambroise, Ivan Ktorza, Alessandro Brombin, Ghaith Abdessalem, Joanne Edouard, et al.. Fgfr3 Is a Positive Regulator of Osteoblast Expansion and Differentiation During Zebrafish Skull Vault Development. Journal of Bone and Mineral Research, American Society for Bone and Mineral Research, 2020, 35 (9), pp.1782-1797. ⟨10.1002/jbmr.4042⟩. ⟨hal-03257993⟩

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