ABSTRACT
The sclerotome is an embryonic structure that gives rise to various supportive tissues, including the axial skeleton and connective tissues. Despite its significance, the mechanisms underlying sclerotome induction and diversification during embryonic development remain poorly understood. Sclerotome progenitors exhibit transient bmp4 expression and an active response to BMP signaling. Using BMP gain- and loss-of-function tools, we demonstrate that BMP signaling is both necessary and sufficient for sclerotome induction. Furthermore, through mosaic expression of a dominant-negative tool, we show that BMP signaling induces sclerotome fate in a cell-autonomous manner. Interestingly, different populations of sclerotome-derived cells have distinct BMP signaling requirements. Sclerotome-derived notochord-associated cells in the trunk lack any BMP response, and sustained BMP signaling inhibits their differentiation into tenocytes. By contrast, sclerotome-derived fin mesenchymal cells in the fin fold require high levels of BMP signaling for proper morphogenesis. Our findings suggest that dynamic regulation of BMP signaling is crucial for the induction of the sclerotome and the subsequent diversification of sclerotome-derived lineages in zebrafish.
Footnotes
Author contributions
Conceptualization: L.X., R.C.M., P.H.; Data curation: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.; Formal analysis: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.; Funding acquisition: P.H.; Investigation: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.; Methodology: L.X., R.C.M., P.H.; Project administration: P.H.; Resources: P.H.; Supervision: P.H.; Validation: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.; Visualization: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.; Writing – original draft: L.X., P.H.; Writing – review & editing: L.X., R.C.M., K.M.K., E.E.M.-O., P.H.
Funding
This study was supported by grants to P.H. from the Canadian Institutes of Health Research (PJT-169113), the Canada Foundation for Innovation John R. Evans Leaders Fund (Project 32920), and a Startup Fund from the Alberta Children's Hospital Research Institute (ACHRI).
Data and resource availability
All relevant data and details of resources can be found within the article and its supplementary information.