A bow-tie genetic architecture for morphogenesis suggested by a genome-wide RNAi screen in Caenorhabditis elegans

During animal development,cellular morphogenesis plays a fundamental role in determining the shape and function of tissues and organs. identifying the components that regulate and drive morphogenesis is thus a major goal of developmental biology. the four-celled tip of the caenorhabditis elegans male tail is a simple but powerful model for studying the mechanism of morphogenesis and its spatiotemporal regulation. here,through a genome-wide post-embryonic rnai-feeding screen,we identified 212 components that regulate or participate in male tail tip morphogenesis. we constructed a working hypothesis for a gene regulatory network of tail tip morphogenesis. we found regulatory roles for the posterior hox genes nob-1 and php-3,the tgf-β pathway,nuclear hormone receptors (e.g. nhr-25),the heterochronic gene blmp-1,and the gata transcription factors egl-18 and elt-6. the majority of the pathways converge at dmd-3 and mab-3. in addition,nhr-25 and dmd-3/mab-3 regulate each others' expression,thus placing these three genes at the center of a complex regulatory network. we also show that dmd-3 and mab-3 negatively regulate other signaling pathways and affect downstream cellular processes such as vesicular trafficking (e.g. arl-1,rme-8) and rearrangement of the cytoskeleton (e.g. cdc-42,nmy-1,and nmy-2). based on these data,we suggest that male tail tip morphogenesis is governed by a gene regulatory network with a bow-tie architecture. © 2011 nelson et al.