Early myotome specification regulates PDGFA expression and axial skeleton development

Reciprocal defects in signaling between the myotome and the sclerotome comp artments of the somites in PDGFR alpha and Myf5 mutant embryos lead to alte rations in the formation of the vertebrae and the ribs. To investigate the significance of these observations, we have examined the role of PDGF signa ling in the developing somite, PDGFA ligand expression was not detected in the myotome of Myf5 null mutant embryos and PDGFA promoter activity was reg ulated by Myf5 in vitro. PDGFA stimulated chondrogenesis in somite micromas s cultures as well as in embryos when PDGFA was knocked into the Myf5 locus , resulting in increased vertebral and rib development. PDGFA expression in the myotome was fully restored in embryos in which MyoD has been introduce d at the Myf5 locus but to a lesser extent in similar myogenin knock-in emb ryos. These results underscore the importance of growth factor signaling wi thin the developing somite and suggest an important role for myogenic deter mination factors in orchestrating normal development of the axial skeleton.