The genetic architecture of male tail tip morphogenesis 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 C. 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-beta 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 the central regulators of tail tip morphogenesis dmd-3 and mab-3. We also showed that DMD-3 and MAB-3 negatively regulate other signaling pathways and affect downstream cellular processes such as vesicular trafficking (i.e. arl-1), endocytosis (i.e. rme-8), and rearrangement of the cytoskeleton (i.e. cdc-42, nmy-1 and nmy-2). Thus, our data support a bow tie genetic architecture for tail tip morphogenesis.