Wnt Signaling and Vertebrate embryogenesis

Wnt 信号传导和脊椎动物胚胎发生

• 批准号: 10546454
• 负责人: Xi He
• 金额: $ 73.41万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546454
• 关键词: Address; Biochemical; Biology; CRISPR screen; Cancer Biology; Cell Communication; Cell Differentiation process; Cell Polarity; Cell Proliferation; Cells; Complex; Congenital Abnormality; Degenerative Disorder; Development; Developmental Biology; Disease; Embryo; Embryonic Development; Family; Health; Homeostasis; Human; Investigation; Malignant Neoplasms; Modeling; Molecular; Pathway interactions; Pattern; Proteomics; Rana; Research; Role; Signal Transduction; Signaling Protein; Tissues; WNT Signaling Pathway; Wnt proteins; Xenopus; experimental study; genome-wide; human disease; insight; receptor; transcriptomics

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.

项目概要/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 信号传导与人类疾病有关，包括出生缺陷、癌症和退行性疾病 失调。 Wnt信号传导机制的研究对于发育和发育具有重要意义 癌症生物学和人类健康，并将揭示疾病治疗的新途径。过去两年 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 调节复杂组装和下游的复杂和各种分子和机制 信号传导，以及 Wnt 通路调节胚胎模式和细胞极性的机制 爪蟾胚胎。 在本申请中，我计划解决有关 Wnt 信号传导机制及其在疾病中的作用的基本问题。 通过采用全基因组 CRISPR/Cas9 筛选、蛋白质组学和 转录组分析与经典的生化和胚胎学方法相结合。 我相信本应用中概述的实验将显着增强我们对 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/疾病产生广泛影响 生物学。