Building a gene regulatory network-based model for cell fate specification and morphogenesis using a new mollusc model.

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PARENT GRANT ABSTRACT Cells are the fundamental units of all biological structures and phenomena—the evolution of novel phenotypes and physiologies is ultimately the result of changes in cellular characteristics, especially cell fate specification. Cell fate specification is well understood in established model systems, and can be described and modelled by building gene regulatory networks (GRNs). It is not well-understood how gene regulatory networks maintain vs modify their wiring over evolution, by making and breaking connections between genes. One of the impediments to making progress in this area is the lack of sophisticated GRNs outside of deuterostomes (echinoderms, vertebrates, ascidians) and ecdysozoans (nematodes and arthropods). Unlike these two well-studied clades, the Spiralia/Lophotrochozoa has not been used for GRN analysis, despite the fact that this monophyletic group includes ~40% of extant animal body plans, including familiar taxa like annelids and molluscs. Many members of the Spiralia begin development with a common ground plan sharing a highly stereotyped pattern of spiral cleavage and homologous cell lineages. Between these species, cell lineages can be homologized at single-cell resolution across hundreds of millions of years of evolution. Yet Spiralian embryos ultimately are transformed through morphogenesis into a vast array of diverse adult body plans. Nowhere else can one undertake systematic comparisons at a single-cell level between body plans; thus spiralians offer a unique opportunity for comparative developmental biology at the level of morphology, molecular mechanisms, and homologous cell lineages. This proposal argues that the slipper snail Crepidula is poised to make significant contributions to GRN biology by being used to build the first developmental GRN among Spiralians. We outline a strategy to build a comprehensive developmental gene regulatory network for every cell type in Crepidula. This research will define: 1) the molecular mechanisms controlling the formation and function of the Crepidula embryonic organizer and 2) the GRN controlling gastrulation. Studying cell fate specification and morphogenesis in a wider range of animals will provide fresh insight into the ways GRNs operate, and will provide a useful comparison for other model systems.