Pdgfab/Pdgfra-mediated chemoattraction guides the migration of sclerotome-derived fibroblast precursors in zebrafish

Abstract

In vertebrates, the sclerotome is a transient embryonic structure that gives rise to various tissue support cells, including fibroblasts. However, how fibroblast precursors are guided to diverse tissues remain poorly understood. Using zebrafish, our lab has previously shown that sclerotome-derived cells undergo extensive migration to generate distinct fibroblast subtypes, including tenocytes along the myotendinous junction and fin mesenchymal cells in the fin fold. The pan-fibroblast gene platelet-derived growth factor receptor a (pdgfra), which has been implicated in cell migration across various contexts, is specifically expressed in the sclerotome and its descendants. Loss of functional Pdgfra in a pdgfra gene-trap mutant results in severe defects in the migration of sclerotome-derived cells, leading to a dose-dependent loss of tenocytes and fin mesenchymal cells. By combining live imaging and mosaic labeling with a membrane-bound dominant-negative tool, we demonstrate that Pdgfra acts cell-autonomously to regulate the migration of sclerotome-derived cells. In the absence of ligand pdgfab, which is expressed in the medial somite, sclerotome-derived cells fail to migrate medially, resulting in a loss of tenocytes, although they can migrate normally toward the fin fold and generate fin mesenchymal cells. Strikingly, localized expression of Pdgfab in pdgfab mutants can direct the migration of sclerotome-derived cells to both normal and ectopic locations, suggesting a chemoattractive role for the Pdgfab ligand. Together, our results demonstrate that Pdgfab/Pdgfra-mediated chemoattraction guides the migration of sclerotome-derived fibroblast precursors to specific locations, where they diversify into distinct fibroblast subtypes.