POZ-ZF Transcription Factors in Signal Transduction and Development.

POZ-ZF 信号转导和发育中的转录因子。

• 批准号: RGPIN-2015-06442
• 负责人: Daniel, Juliet
• 金额: $ 2.48万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614152
• 关键词: POZ; ZF; Transcription; Factors; Signal

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. These events require communication between cells via a phenomenon called signal transduction, which often culminates 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 the crucial stages of early vertebrate development, it is unclear how these various signals are integrated to elicit the specific cellular responses needed for this process. Recently several members of the family of POZ-zinc finger (POZ-ZF) transcription factors have been linked to signaling pathways that are essential for vertebrate development. Additionally, data from my laboratory revealed that frog embryos lacking different POZ-ZF proteins displayed striking early and late developmental defects. These observations led to our hypothesis that POZ-ZF proteins are important effectors of signaling transduction during early vertebrate development. Since little is known about how POZ-ZF proteins are mechanistically connected to established signaling pathways, our Discovery research program focuses on deciphering "The Role and Basic Mechanisms of Action of POZ-ZF Transcription Factors in Vertebrate Development" using the frog Xenopus laevis as a model organism. Xenopus is a proven model system for such studies because frogs are inexpensive, the embryos are very easy to manipulate for protein knockdown and overexpression studies, and the Xenopus versions of the mammalian POZ-ZF proteins we are studying are very similar. To achieve our research goals, we will utilize a variety of cutting-edge and established molecular cell biology skills that are essential for success in the Canadian and International biology research arena.

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。这些事件需要细胞之间通过一种称为信号转导的现象进行交流，这种现象通常在细胞核中达到高潮，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，并分裂，分化或变得能动。虽然已经确定了几个信号通路，调节早期脊椎动物发育的关键阶段，目前还不清楚这些不同的信号是如何整合，以引起这一过程所需的特定细胞反应。最近，POZ-锌指（POZ-ZF）转录因子家族的几个成员已被连接到脊椎动物发育所必需的信号通路。此外，我实验室的数据显示，缺乏不同POZ-ZF蛋白的青蛙胚胎显示出明显的早期和晚期发育缺陷。这些观察结果导致我们的假设，POZ-ZF蛋白是在早期脊椎动物发育过程中的信号转导的重要效应。由于对POZ-ZF蛋白如何与已建立的信号通路机械连接知之甚少，我们的发现研究计划侧重于使用青蛙非洲爪蟾作为模式生物来破译“POZ-ZF转录因子在脊椎动物发育中的作用和基本作用机制”。非洲爪蟾是一个经过验证的模型系统，因为青蛙是廉价的，胚胎是非常容易操纵的蛋白质敲低和过表达的研究，和非洲爪蟾版本的哺乳动物POZ-ZF蛋白，我们正在研究的是非常相似的。为了实现我们的研究目标，我们将利用各种尖端和既定的分子细胞生物学技能，这些技能对于在加拿大和国际生物学研究竞技场取得成功至关重要。