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

Developmental programs that govern the embryonic diversification of distinct kinds of muscles in vertebrates remain obscure. For instance, the most widely recognized attribute of early diversity among skeletal myoblasts is their ability to differentiate exclusively into fibers with slow or fast contractile properties. However, we know little about the developmental basis and 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 that regulates the choice of myoblasts to adopt slow versus fast fiber developmental pathways. In u-boot mutant embryos, slow muscle precursors abort their developmental program, failing to activate expression of the homeobox gene prox1 and transfating into muscle cells with fast fiber properties. Using oligonucleotide-mediated translational inhibition, we have investigated the role of prox1 in this program. We find that it functions in the terminal step of the u-boot controlled slow fiber developmental pathway in the regulation of slow myofibril assembly. Our findings provide new insight into the genetic control of slow versus fast fiber specification and differentiation and indicate that dedicated developmental pathways exist in vertebrates for the elaboration of distinct elements of embryonic muscle pattern.