Wnt Signaling and Vertebrate embryogenesis

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Project Summary/Abstract The Wnt family of secreted signaling proteins governs embryogenesis and tissue homeostasis. Deregulated Wnt signaling has been implicated in human diseases including birth defects, cancer, and degenerative disorders. Investigation of the mechanism of Wnt signaling has critical significance for developmental and cancer biology and human health, and will uncover new avenues for disease treatment. Over the last two decades, research in my lab has elucidated many key aspects of the Wnt pathway, including the Wnt receptor complex and various molecules and mechanisms that regulate the complex assembly and downstream signaling, and the mechanism by which the Wnt pathway regulates embryonic patterning and cell polarity in Xenopus embryos. In this application I plan to address fundamental questions on the mechanism of Wnt signaling and its role in vertebrate early embryogenesis by employing genome-wide CRISPR/Cas9 screening, proteomic and transcriptomic analyses in combination with classical biochemical and embryological approaches. I believe that experiments outlined in this application will significantly enhance our understanding of Wnt signaling and early vertebrate embryogenesis, and have broad impact to developmental and cancer/disease biology.