Biology subjects

Malbouyres, M.

Publications and source records attributed to Malbouyres, M..

2 recordsLinked to original sources

bioRxiv2025

Cranial suture integrity is maintained by Fgfr3 in zebrafish

Cranial suture formation is a dynamic process requiring precise cellular and molecular coordination to regulate bone growth and suture homeostasis. Despite the recognized role of Fibroblast Growth Factor Receptor 3 (FGFR3) in this process and its association with Muenke syndrome, one of the most common syndromic craniosynostoses, its precise function remains undefined. Through analyses of cranial suture formation and maintenance in a fgfr3 LoF zebrafish model displaying abnormal suture morphology, we demonstrate for the first time that Fgfr3 plays a pleiotropic role during these events. Transmission electron microscopy and second harmonic generation imaging revealed that Fgfr3 is involved in the proper organization of the collagen network within the suture. By employing specific transgenic reporter lines and studying gene expression of suture mesenchymal stem cell markers via RNAscope in situ hybridization, we show that Fgfr3 is crucial for regulating osteogenesis within the suture. Specifically, Fgfr3 limits the number of osteoprogenitors at the osteogenic front and promotes osteoblast maturation at the suture edge. Finally, our results reveal that Fgfr3-mediated regulation of osteogenesis involves cross-talk between FGF, canonical Wnt, and potentially BMP signaling pathways. In conclusion, these data position Fgfr3 as a central regulator of cranial suture formation and open new perspectives for understanding suture homeostasis and FGFR3-related craniosynostoses.

developmental biology↗

bioRxiv2021

The myotendinous junction marker collagen XXII enables zebrafish postural control learning and optimal swimming performance through its force transmission activity

Although the myotendinous junction (MTJ) is essential for skeletal muscle integrity, its contribution to skeletal muscle function remains largely unknown. Here, we show that CRISPR-Cas9-mediated gene ablation of the MTJ marker col22a1 in zebrafish identifies two distinctive phenotypic classes: class 1 individuals reach adulthood with no overt muscle phenotype while class 2 display severe movement impairment and eventually dye before metamorphosis. Yet mutants that are unequally affected are all found to display defective force transmission attributed to a loss of ultrastructural integrity of the MTJ and myosepta, though with distinct degrees of severity. The behavior-related consequences of the resulting muscle weakness similarly reveal variable phenotypic expressivity. Movement impairment at the critical stage of swimming postural learning eventually causes class 2 larval death by compromising food intake while intensive exercise is required to uncover a decline in muscle performance in class 1 adults. By confronting MTJ gene expression compensation and structural, functional and behavioral insights of MTJ dysfunction, our work unravels variable expressivity of col22a1 mutant phenotype. This study also underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.

developmental biology↗