Fgfr3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development

AbstractGain 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 offgfr3 during skull development; in order to study FGFR3 ’s role in cranial vault development, we generated the firstfgfr3 loss ‐of‐function zebrafish(fgfr3lof/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 zebrafishfgfr3lof/lof revealed a delay in osteoblast expansion and differentiation, together with changes in the extracellular matrix. These findings demonstrate thatfgfr3 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.

Source: Journal of Bone and Mineral Research - May 6, 2020 Category: Orthopaedics Authors: Emilie Dambroise, Ivan Ktorza, Alessandro Brombin, Ghaith Abdessalem, Joanne Edouard, Marine Luka, Imke Fiedler, Olivia Binder, Olivier Pelle, E. Elizabeth Patton, Bj örn Busse, Mickaël Menager, Frederic Sohm, Laurence Legeai‐Mallet Tags: Original Article Source Type: research