cdonandbocaffect trunk neural crest cell migration non-cell autonomously through a reduction of hedgehog signaling in zebrafish slow-twitch muscle

AbstractThe transmembrane proteinscdonandbocare implicated in regulating hedgehog signaling during vertebrate development. Recent work showing roles for these genes in axon guidance and neural crest cell migration suggest thatcdon/bocmay play additional functions in regulating directed cell movements. We use novel and existing mutants to investigate a role forcdonandbocin zebrafish neural crest cell migration. We find that single mutant embryos exhibit normal neural crest phenotypes, but that neural crest migration is strikingly disrupted in doublecdon;bocmutant embryos. We further show that this migration phenotype is associated with defects to the differentiation of slow-twitch muscle cells, and the loss of a Col1a1a containing extracellular matrix, suggesting that neural crest defects are a secondary consequence to defects in mesoderm development. Combined, our data add to a growing literature showing thatcdonandbocact synergistically to promote hedgehog signaling during vertebrate development, and provide a foundation for using zebrafish to study the function of hedgehog receptor paralogs.