Positive and Negative Regulation of Muscle Cell Identity by Members of the Hedgehog and TGF-Î2 Gene Families

We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGFb signals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite. Ectopic expression in the notochord of Dorsalin-1, a member of the TGFb superfamily, inhibits the formation of muscle pioneer cells, demonstrating that TGFb signals can antagonize the induction of muscle pioneer cells by Hedgehog. We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGFb signals exert competing positive and negative influences on the development of muscle