A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in Caenorhabditis elegans

Matthew D Nelson,David H A Fitch,Karin Kiontke,Khushbu Shah,Hélène Fradin,Daniel Martin,Grayson Maldonado,Elinor Zhou,Andrew D Chisholm

doi:10.1371/journal.pgen.1002010

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.

Highlights

Morphogenesis involves the coordinated change in the shape of cells and tissues during development, eventually giving rise to functional structures in the adult animal
Genome-wide RNAi screen identifies 212 candidate genes involved in male tail tip morphogenesis
We have presented evidence that the genetic network underlying C. elegans male tail tip morphogenesis is consistent with a bow-tie architecture in which dmd-3, mab-3 and nhr-25 are the central regulators in a conserved core (Figure 8)

Summary

Introduction

Morphogenesis involves the coordinated change in the shape of cells and tissues during development, eventually giving rise to functional structures in the adult animal. Such coordinated change must occur at the correct time and in the proper position. The model we use is the male tail tip of Caenorhabditis elegans This structure is made up of four epithelial ("hypodermal") cells, hyp8–hyp, which are born during embryogenesis. The tail tip model allows the study of a sexual dimorphism at the cellular level Another advantage of this model is that male-specific mutations in C. elegans can be propagated through the self-fertile hermaphrodites, even if the mutations affect male fertility, mating ability, or viability

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Discussion

Conclusion