POZ-ZF transcription factors in cell adhesion 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。细胞间的黏附和细胞内的信号转导等事件在细胞核内达到顶峰，基因表达的变化由称为转录因子的蛋白质控制。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。虽然已经确定了几个调节原肠形成的信号通路，原肠形成是早期发育中的一个关键事件，但不清楚各种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，至少有两个POZ-ZF(POZ-ZF)转录因子与Wnt信号通路相连，这是脊椎动物发育所必需的。这导致了我们的假设，POZ-ZF蛋白在脊椎动物早期胚胎发育中整合重要的信号级联过程中发挥作用。我们的研究计划试图了解“POZ-ZF转录因子家族在细胞黏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利用非洲爪蛙作为模式生物来阐明脊椎动物POZ-ZF蛋白的发育作用。非洲爪蛙是一个很好的模型系统，因为蛙类价格低廉，易于操纵，用于蛋白质敲除和过度表达的研究，而且非洲爪蛙与许多哺乳动物POZ-ZF蛋白有同源关系，与发育有关。实验室的初步数据显示，缺乏不同POZ-ZF蛋白的青蛙胚胎表现出显著的早期发育缺陷，支持它们在脊椎动物早期发育中发挥重要作用的假说。提出的研究将为脊椎动物早期发育和原肠发育提供新的见解，并增加关于POZ-ZF蛋白在整个脊椎动物中功能的知识库。

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.