Characterization of Pak kinase regulation of epithelial morphogenesis during Drosophila oogenesis

Rho家族的小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。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，我们正在了解Pak如何调节上皮细胞的发育。我们多年来一直在研究的一个功能是Pak如何调节一种称为肌动球蛋白细胞骨架的收缩结构来控制上皮细胞的形状。我们一直在解开与Pak一起控制卵泡上皮细胞形状的复杂蛋白质网络，并将在拟议的资金下继续这项工作。我们要讨论的Pak的第二个功能是它如何参与子房中一个叫做基柄的重要结构的形成。基茎本质上是一个圆盘状上皮细胞堆叠在一起的“塔”，就像一堆硬币。这种结构是由一种叫做细胞嵌入的过程形成的，这种过程被广泛用于延长胚胎发育过程中的组织，包括脊椎动物。因此，我们对基柄形成的了解可以应用于理解不同生物的胚胎发育。总的来说，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这些疾病中哪些过程是有缺陷的。

The Rho family 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. 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 are learning how Pak regulates epithelial development. One Pak function we have been studying for a number of years is how Pak regulates a contractile structure called the actomyosin cytoskeleton to control epithelial cell shape. We have been unraveling the complex network of proteins working with Pak in controlling cell shape in the follicular epithelium and will continue this work with the proposed funding. The second function for Pak we will address is how it participates in formation of a remarkable structure called the basal stalk in the ovary. The basal stalk is essentially a "tower" of disc-shaped epithelial cells stacked on top of one another rather like a stack of coins. This structure is formed by a process called cell intercalation, which is widely used to elongate tissues during embryonic development, including in vertebrates. Thus, what we learn about basal stalk formation could be applied to understanding embryonic development in diverse organisms. Overall, the proposed work will be of interest to both 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 processes are defective in such disorders.