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

Abstract

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.