PT  - JOURNAL ARTICLE
AU  - Emilie Dambroise
AU  - Ivan Ktorza
AU  - Alessandro Brombin
AU  - Ghaith Abdessalem
AU  - Joanne Edouard
AU  - Marine Luka
AU  - Imke Fiedler
AU  - Olivia Binder
AU  - Olivier Pelle
AU  - E. Elizabeth Patton
AU  - Björn Busse
AU  - Mickaël Menager
AU  - Frederic Sohm
AU  - Laurence Legeai-Mallet
TI  - FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development
AID  - 10.1101/2020.01.02.884155
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.02.884155
4099  - http://biorxiv.org/content/early/2020/01/02/2020.01.02.884155.short
4100  - http://biorxiv.org/content/early/2020/01/02/2020.01.02.884155.full
AB  - 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 (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 zebrafish fgfr3lof/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 hypothesize that changes in the extracellular matrix within growing bone impair cell-cell communication, mineralization, and new osteoblast recruitment.