Early myotome specification regulates PDGFA expression and axial skeleton development.
Reciprocal defects in signaling between the myotome and the sclerotome compartments of the somites in PDGFRalpha and Myf5 mutant embryos lead to alterations in the formation of the vertebrae and the ribs. To investigate the significance of these observations, we have examined the role of PDGF signaling in the developing somite. PDGFA ligand expression was not detected in the myotome of Myf5 null mutant embryos and PDGFA promoter activity was regulated by Myf5 in vitro. PDGFA stimulated chondrogenesis in somite micromass 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 introduced at the Myf5 locus but to a lesser extent in similar myogenin knock-in embryos. These results underscore the importance of growth factor signaling within the developing somite and suggest an important role for myogenic determination factors in orchestrating normal development of the axial skeleton.
Tallquist
M D
MD
Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Weismann
K E
KE
Hellström
M
M
Soriano
P
P
D000483:Alleles; D000818:Animals; D001842:Bone and Bones / Q000196:embryology*; D020219:Chondrogenesis; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D015534:Trans-Activators
D004268:DNA-Binding Proteins; C497417:MYF5 protein, human; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D010982:Platelet-Derived Growth Factor; D015534:Trans-Activators; C075278:platelet-derived growth factor A