Characterization of Pak kinase regulation of epithelial morphogenesis during Drosophila oogenesis

Rho家族的小GTP酶充当分子开关，在“开”和“关”状态之间循环。它们将信息传递到细胞内，并通过Pak等蛋白质调节细胞形状和细胞运动。上皮是包括皮肤和内脏成分的细胞片，在动物的发育过程中是非常重要的组织。在上皮细胞的形成过程中，Rho家族和Pak帮助将这些组织塑造成它们的最终形状。我们正在用果蝇来研究Pak调节上皮发育的基因特征。果蝇是一种受欢迎的研究生物，这是因为为研究它而开发的先进技术，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滤泡上皮，这是一种覆盖着发育中的卵子的典型上皮。利用这个系统，我们正在了解Pak是如何调节上皮发育的。多年来，我们一直在研究Pak的一个功能是Pak如何调节一种称为肌动蛋白细胞骨架的收缩结构，以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，并将利用拟议的资金继续这项工作。我们将讨论的PAK的第二个功能是它如何参与卵巢中一种叫做基柄的显着结构的形成。基柄本质上是一座盘状上皮细胞的“塔”，彼此堆叠在一起，就像一堆硬币。这种结构是通过一种称为细胞嵌入的过程形成的，这种过程广泛用于在胚胎发育期间延长组织，包括在脊椎动物中。因此，我们所学到的关于基柄形成的知识可以应用于了解不同生物体的胚胎发育。总体而言，发育生物学家和细胞生物学家都会对拟议的工作感兴趣，此外，上皮发育不当是导致各种出生缺陷的原因之一，我们的工作可能会深入了解此类疾病的哪些过程存在缺陷。

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.