Functional mapping of Rho GTPase regulatory machineries controlling C. elegans embryonic development

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In multicellular organisms, embryonic development is dependent on a continuous flow of information through a complex network of cells. The ability of signaling machinery to integrate multiple upstream signals is critical in the control of cellular behavior. However, these mechanisms are still poorly understood. Rho GTPases together with proteins regulating their enzymatic activity (regulators), are signal transduction proteins involved downstream of a wide range of receptors. They are consequently considered as key players in cell signaling integration. However, despite extensive effort, functional characterization of individual GTPases and regulators has not been able to describe how these genes coordinate their function in order to integrate intercellular signals. To address this issue, we will use the microscopic hearth worm, Caenorhabditis elegans, as a model system to produce a spatiotemporal map of Rho-specific regulatory machineries controlling embryonic development. To do so, we will develop an integrative genomics approach consisting in the generation and integration of complementary layers of biological information. Our integrative approach will produce the first dynamic model of Rho GTPase regulation in a multicellular organism. This model will be subsequently used as a backbone to better understand how interaction of Rho-regulatory machineries with upstream and downstream signaling modules could direct cell signaling integration events during embryonic development. Construction of such a model will significantly contribute to a comprehensive mapping of cell signaling events during complex and dynamic biological processes. Moreover, Rho GTPases and their regulators are extremely well conserved between nematode and human. They are also involved in number of human pathologies. Our research program will consequently provide the scientific community with dynamic models that could be used to better understand the behavior of cell signaling machineries during normal human development as well as in pathological context.