POZ-ZF transcription factors in cell adhesion and development

POZ-ZF 转录因子在细胞粘附和发育中的作用

• 批准号: 238700-2010
• 负责人: Daniel, Juliet
• 金额: $ 2.91万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=547066
• 关键词: POZ; ZF; transcription; factors; cell

The development of multicellular organisms involves a highly coordinated and controlled series of events that regulates the proliferation and differentiation of cells into tissues and organs with specific functions. Events such as cell-cell adhesion and signal transduction within cells culminate in the nucleus with changes in gene expression controlled by proteins called transcription factors. These changes in gene expression in turn trigger cells to respond and either divide, differentiate, or become motile. Although several signaling pathways have been identified that regulate gastrulation, a key event in early development, it is unclear how the various signals are integrated to elicit the specific cellular responses needed for this process. Recently at least two POZ-zinc finger (POZ-ZF) transcription factors have been linked to Wnt signaling pathways that are absolutely required for vertebrate development. This led to our hypothesis that POZ-ZF proteins play a role in integrating important signaling cascades during early vertebrate embryogenesis. Our research program seeks to understand "The Role and Basic Mechanisms of Action of the POZ-ZF family of Transcription Factors in Cell Adhesion and Vertebrate Development". Our Discovery Grant focuses on elucidating the developmental role of vertebrate POZ-ZF proteins using the frog Xenopus laevis as a model organism. Xenopus is a good model system because frogs are inexpensive, easy to manipulate for protein knockdown and overexpression studies and there are Xenopus homologs to many of the mammalian POZ-ZF proteins implicated in development. Preliminary data from my laboratory revealed that frog embryos lacking different POZ-ZF proteins displayed striking early developmental defects, supporting the hypothesis that they play an important role in early vertebrate development. The proposed studies will provide novel insight on early vertebrate development and gastrulation, and add to the knowledge base of POZ-ZF protein function in vertebrates as a whole.

多细胞生物体的发育涉及一系列高度协调和受控的事件，这些事件调节细胞增殖和分化成具有特定功能的组织和器官。细胞内的细胞间粘附和信号转导等事件在细胞核中达到顶峰，基因表达的变化由称为转录因子的蛋白质控制。这些基因表达的变化反过来触发细胞做出反应，要么分裂，分化，要么变得能动。虽然已经确定了几个信号通路，调节原肠胚形成，在早期发育的关键事件，目前还不清楚如何整合各种信号，以引起这一过程所需的特定细胞反应。最近，至少有两个POZ-锌指（POZ-ZF）转录因子已被连接到Wnt信号通路，是脊椎动物发育所必需的。这导致了我们的假设，POZ-ZF蛋白在整合早期脊椎动物胚胎发生过程中的重要信号级联发挥作用。我们的研究项目旨在了解“POZ-ZF转录因子家族在细胞粘附和脊椎动物发育中的作用和基本作用机制”。我们的发现基金专注于阐明脊椎动物POZ-ZF蛋白的发育作用，使用青蛙非洲爪蟾作为模式生物。非洲爪蟾是一个很好的模型系统，因为青蛙是廉价的，易于操作的蛋白质敲低和过表达的研究，有非洲爪蟾同源物的许多哺乳动物POZ-ZF蛋白参与发展。来自我实验室的初步数据显示，缺乏不同POZ-ZF蛋白的青蛙胚胎显示出显著的早期发育缺陷，支持它们在早期脊椎动物发育中发挥重要作用的假设。这些研究将为脊椎动物早期发育和原肠胚形成提供新的见解，并为整个脊椎动物中POZ-ZF蛋白功能的知识基础提供补充。