The u-boot mutation identifies a Hedgehog-regulated myogenic switch for fiber-type diversification in the zebrafish embryo

Developmental programs that govern the embryonic diversification of distinc t kinds of muscles in vertebrates remain obscure. For instance, the most wi dely recognized attribute of early diversity among skeletal myoblasts is th eir ability to differentiate exclusively into fibers with slow or fast cont ractile properties. However, we know little about the developmental basis a nd genetic regulation of this seminal event in vertebrate myogenesis. Here we show that in the zebrafish, the u-boot gene acts as a myogenic switch th at regulates the choice of myoblasts to adopt slow versus fast fiber develo pmental pathways. In u-boot mutant embryos, slow muscle precursors abort th eir developmental program, failing to activate expression of the homeobox g ene prox1 and transfating into muscle cells with fast fiber properties. Usi ng oligonucleotide-mediated translational inhibition, we have investigated the role of prox1 in this program. We find that it functions in the termina l step of the u-boot controlled slow fiber developmental pathway in the reg ulation of slow myofibril assembly. Our findings provide new insight into t he genetic control of slow versus fast fiber specification and differentiat ion and indicate that dedicated developmental pathways exist in vertebrates for the elaboration of distinct elements of embryonic muscle pattern.