Characterization of pak kinase function in drosophila oogenesis

Rho家族与ras相关的小gtpase充当分子开关，在“开”和“关”状态之间循环。它们将信息传递到细胞中，并通过Pak等蛋白质调节细胞形状和细胞运动。上皮细胞是一层细胞，包括皮肤和内部器官的组成部分，是动物发育中非常重要的组织。在上皮形成过程中，Rho家族和Pak帮助这些组织形成最终的形态。人们对Rho家族和Pak的了解大多来自于对培养细胞的研究，而对这些蛋白质在完整生物体中的作用知之甚少。我们正在使用果蝇来遗传表征Pak调节上皮发育的机制。果蝇是一种受欢迎的研究生物，因为研究它的先进技术已经开发出来，包括非常复杂的遗传工具，以及在整个动物的背景下在细胞水平上对事件进行详细成像的能力。我们一直在观察卵巢中的卵泡上皮，这是一种覆盖在发育中的卵子上的典型上皮。利用这个系统，我们希望深入了解Pak如何调节上皮发育的三个重要过程。第一个过程是调节细胞粘附，这是决定细胞如何“粘”在一起形成组织的关键。第二种是通过调节一种叫做肌动球蛋白细胞骨架的收缩结构来调节上皮细胞的形状。最后，我们想知道Pak如何调节上皮细胞的增殖。其他实验室先前的研究已经确定了调节这三个过程的各种蛋白质，我们怀疑Pak可能通过改变它们的活性与这些其他蛋白质相互作用。我们将使用遗传学和生物化学来解决Pak和这些上皮发育的其他调节因子之间的关系。这项工作将引起发育生物学家和细胞生物学家的兴趣，此外，上皮细胞发育不当是各种出生缺陷的原因，我们的工作可能会深入了解在这些疾病中是什么细胞信号通路缺陷。

The Rho family of Ras-related small GTPases act as molecular switches, cycling between "on" and "off" states. They convey information into the cell and regulate cell shape and cell movement through proteins such as Pak. Epithelia are sheets of cells that include the skin and components of internal organs and are very important tissues in the development of animals. During the formation of epithelia, the Rho family and Pak help shape these tissues into their final configuration. Much of what is known about the Rho family and Pak has been come from studying cultured cells and relatively little is known about how these proteins operate in an intact organism. We are using the fruit fly Drosophila to genetically characterize the mechanisms by which Pak regulates epithelial development. Drosophila is a popular research organism due to the advanced techniques that have been developed for studying it, including very sophisticated genetic tools and the ability to do detailed imaging of events at the cellular level within the context of a whole animal. We have been looking at the follicular epithelium in the ovary, a typical epithelium that covers the developing egg. Using this system, we hope to gain insight into how Pak regulates three important processes in epithelial development. The first process is the regulation of cell adhesion, which is critical in determing how cells "stick" together to form tissues. The second is the regulation of epithelial cell shape through regulation of a contractile structure called the actomyosin cytoskeleton. Finally, we want to known how Pak regulates the proliferation of epithelial cells. Previous studies in other laboratories have identified various proteins regulating these three processes and we suspect that Pak interacts with these other poteins, perhaps by modifying their activity. We will use both genetics and biochemistry to address the relationship between Pak and these other regulators of epithelial development. This work will be of interest to developmental biologists and cell biologists, furthermore, improper development of epithelia is a cause of diverse birth defects, and our work may yield insight into what cell signaling pathways are defective in such disorders.