MYOD AND MYF-5 DIFFERENTIALLY REGULATE THE DEVELOPMENT OF LIMB VERSUSTRUNK SKELETAL-MUSCLE

The myogenic progenitors of epaxial (paraspinal and intercostal) and h ypaxial (limb and abdominal wall) musculature are believed to originat e in dorsal-medial and ventral-lateral domains, respectively, of the d eveloping somite, To investigate the hypothesis that Myf-5 and MyoD ha ve different roles in the development of epaxial and hypaxial musculat ure, we further characterized myogenesis in Myf5- and MyoD-deficient e mbryos by several approaches, We examined expression of a MyoD-lacZ tr ansgene in Myf-5 and MyoD mutant embryos to characterize the temporal- spatial patterns of myogenesis in mutant embryos, In addition, we perf ormed immunohistochemistry on sectioned Myf-5 and MyoD mutant embryos with antibodies reactive with desmin, nestin, myosin heavy chain, sarc omeric actin, Myf-5, MyoD and myogenin. While MyoD(-/-) embryos displa yed normal development of paraspinal and intercostal muscles in the bo dy proper, muscle development in limb buds and brachial arches was del ayed by about 2.5 days, By contrast, Myf-5(-/-) embryos displayed norm al muscle development in limb buds and brachial arches, and markedly d elayed development of paraspinal and intercostal muscles, Although Myo D mutant embryos exhibited delayed development of limb musculature, no rmal migration of Pax-3-expressing cells into the limb buds and normal subsequent induction of Myf-5 in myogenic precursors was observed, Th ese results suggest that Myf-5 expression in the limb is insufficient for the normal progression of myogenic development, Taken together, th ese observations strongly support the hypothesis that Myf-5 and MyoD p lay unique roles in the development of epaxial and hypaxial muscle, re spectively.