title: A bow-tie genetic architecture for morphogenesis suggested by a genome-wide RNAi screen in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Department of Biology, New York University, New York, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Nelson
authors.forename: Elinor
authors.initials: E
authors.lastname: Zhou
authors.forename: Karin
authors.initials: K
authors.lastname: Kiontke
authors.forename: Hélène
authors.initials: H
authors.lastname: Fradin
authors.forename: Grayson
authors.initials: G
authors.lastname: Maldonado
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Khushbu
authors.initials: K
authors.lastname: Shah
authors.forename: David H A
authors.initials: DH
authors.lastname: Fitch
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005801:Genes, Homeobox; D008297:Male; D023421:Models, Animal; D009024:Morphogenesis / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D013623:Tail / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C532001:DMD-3 protein, C elegans; D004268:DNA-Binding Proteins; C110548:Mab-3 protein, C elegans; D014157:Transcription Factors; C486359:nuclear hormone receptor NHR-25, C elegans