Characterization of Pak kinase regulation of epithelial morphogenesis during Drosophila oogenesis

点击翻译按钮获取中文摘要

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.