POZ-ZF Transcription Factors in Signal Transduction and Development.

多细胞生物体的发育涉及一系列高度协调和受控的事件，这些事件调节细胞的增殖和分化成具有特定功能的组织和器官。这些事件需要通过一种称为信号转导的现象在细胞之间进行交流，信号转导通常在细胞核中达到顶峰，由被称为转录因子的蛋白质控制的基因表达发生变化。基因表达的这些变化反过来会触发细胞做出反应，要么分裂、分化，要么变得能动。虽然已经确定了几种信号通路来调节脊椎动物早期发育的关键阶段，但还不清楚这些不同的信号是如何整合在一起的，以引发这一过程所需的特定细胞反应。最近，POZ-ZF转录因子家族中的几个成员被认为与脊椎动物发育所必需的信号通路有关。此外，来自我的实验室的数据显示，缺乏不同POZ-ZF蛋白的青蛙胚胎显示出显著的早期和晚期发育缺陷。这些观察结果导致我们假设POZ-ZF蛋白是脊椎动物早期发育过程中信号转导的重要效应者。由于对POZ-ZF蛋白如何与已建立的信号通路机械联系知之甚少，我们的发现研究计划以非洲爪蛙为模式生物，致力于破译POZ-ZF转录因子在脊椎动物发育中的作用和基本作用机制。非洲爪哇是此类研究的成熟模型系统，因为青蛙价格低廉，胚胎非常容易操作，用于蛋白质敲除和过度表达研究，而且我们研究的哺乳动物POZ-ZF蛋白的非洲爪哇版本非常相似。为了实现我们的研究目标，我们将利用各种尖端和成熟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领域取得成功至关重要。

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.