POSITIVE AND NEGATIVE REGULATION OF MUSCLE-CELL IDENTITY BY MEMBERS OF THE HEDGEHOG AND TGF-BETA GENE FAMILIES

We have examined whether the development of embryonic muscle fiber typ e is regulated by competing influences between Hedgehog and TGF-beta s ignals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or i nhibition 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 TGF-beta superfamily, inhibits the formation of mu scle pioneer cells, demonstrating that TGF-beta 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 c ells, and subsequent Hedgehog and TGF-beta signals exert competing pos itive and negative influences on the development of muscle pioneer cel ls.