Cell polarity and morphogenesis in Xenopus embryos

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Project summary In the early vertebrate embryo, signaling pathways instruct cell fates and orchestrate morphogenetic movements, placing cells into proper positions to experience new rounds of signaling and new waves of fate specification and morphogenesis. A long standing question remains how changes in cell polarity determine collective cell behaviors during early development. To approach this problem, this program focuses on the core planar cell polarity (PCP) pathway that is one of the main drivers of morphogenetic processes in vertebrates. Core PCP proteins have been discovered in Drosophila genetic studies. In vertebrates, the PCP protein complexes Vangl/Pk/Celsr and Fz/Dvl/Celsr are conserved and accumulate at opposite cell edges along the body axis, marking tissue polarity. The significance of the core PCP proteins extends far beyond being epithelial polarity markers, as their vertebrate homologs function in key developmental processes, including gastrulation movements, neural tube closure and branching morphogenesis, the formation of functional cilia and left-right patterning. To gain mechanistic knowledge of morphogenetic events, including vertebrate gastrulation, we will study the following long-standing questions in the field: a) how cells polarize in response to a cue, b) how the cell polarity translates into spatially restricted activation of effectors such as Myosin II, and c) how actomyosin contractions and the resulting mechanical forces alter cell shape and coordinate collective cell movements. New force-dependent genes that are involved in the control of morphogenesis will be identified. These directions will be pursued using high resolution imaging, embryological and molecular biological techniques combined with systems level analysis (proteomics and transcriptomics). Our studies will use Xenopus embryos as our main experimental model, due to their fast external development, ease of experimental manipulation and large size allowing biochemical and systems biology approaches. The proposed studies will advance the knowledge of basic cell biological mechanisms underlying vertebrate morphogenesis. High relevance to human health is due to the known connections of PCP signaling to multiple congenital defects and syndromes, polycystic kidney disease and cancers.