MUSCLE PROGENITOR CELLS FAILING TO RESPOND TO POSITIONAL CUES ADOPT NONMYOGENIC FATES IN MYF-5 NULL MICE

MICE that have mutations in both myogenic transcription factors Myf-5 and MyoD totally lack skeletal muscle fibres and their precursor myobl asts(1), whereas with either mutation alone, muscle is present(2,3). S keletal muscle in the vertebrate body is derived from epithelial somit es that respond to environmental signals to form the dorsal epithelial dermomyotome (dermis, muscle) and ventral mesenchymal sclerotome (axi al skeleton, ribs)(4,5). The first muscle, the myotome, forms centrall y in the somite, when only myf-5 is programming myogenesis. By targeti ng the nlacZ reporter gene into the myf-5 locus, we demonstrate that b eta-galactosidase(+) muscle progenitor cells are present in the dermom yotome of myf-5 null embryos, and that they undergo a normal epithelia l-mesenchymal transition; however, they migrate aberrantly. Dorsally, they accumulate under the ectoderm and express a non-muscle dermal mar ker, Dermo-1, Ventrally, beta-galactosidase(+) cells also fail to loca lize correctly, express a cartilage marker scleraxis, and are subseque ntly found in ribs, Therefore Myf-5 protein is necessary for cells to respond correctly to positional cues in the embryo and to adopt their myogenic fate, In its absence, muscle progenitors, having activated my f-5, remain multipotent and differentiate into other semitic derivativ es according to their local environment.