Wnt Signaling and Vertebrate embryogenesis

项目总结/摘要 分泌信号蛋白的Wnt家族控制胚胎发生和组织稳态。放松管制 Wnt信号转导与人类疾病有关，包括出生缺陷、癌症和退行性疾病。 紊乱Wnt信号转导机制的研究对发育和 癌症生物学和人类健康，并将发现疾病治疗的新途径。过去两 几十年来，我实验室的研究已经阐明了Wnt通路的许多关键方面，包括Wnt受体 复杂和各种分子和机制，调节复杂的组装和下游 信号，以及Wnt途径调节胚胎模式和细胞极性的机制， 非洲爪蟾胚胎 在本申请中，我计划解决Wnt信号传导机制及其在 通过采用全基因组CRISPR/Cas9筛选、蛋白质组学和 转录组学分析与经典的生物化学和胚胎学方法相结合。 我相信，在这个应用程序中概述的实验将大大提高我们对Wnt的理解 信号传导和早期脊椎动物胚胎发生，并对发育和癌症/疾病有广泛的影响 生物学

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.