Characterization of Pak kinase regulation of epithelial morphogenesis during Drosophila oogenesis

果蝇卵子发生过程中 Pak 激酶对上皮形态发生的调节特征

• 批准号: 217532-2013
• 负责人: Harden, Nicholas
• 金额: $ 3.13万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594008
• 关键词: Characterization; Pak; kinase; regulation; epithelial

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.

Rho家族小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中，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部器官的组成部分的细胞片，并且是动物发育中非常重要的组织。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其最终形态。我们正在使用果蝇的遗传特性的机制，Pak调节上皮细胞的发展。果蝇是一种受欢迎的研究生物体，因为已经开发了用于研究它的先进技术，包括非常复杂的遗传工具和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，这是一种典型的上皮，覆盖在发育中的卵子上。使用这个系统，我们正在学习Pak如何调节上皮发育。Pak的一个功能我们已经研究了很多年，它是如何调节一种叫做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一起控制滤泡上皮细胞形状的复杂蛋白质网络，并将继续这项工作。我们将讨论Pak的第二个功能是它如何参与卵巢中称为基柄的显著结构的形成。基底柄基本上是一个由盘状上皮细胞组成的“塔”，这些上皮细胞一个堆叠在另一个的顶部，就像一堆硬币。这种结构是通过一种称为细胞插入的过程形成的，该过程广泛用于在胚胎发育期间延长组织，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体的胚胎发育。总的来说，拟议的工作将是感兴趣的发育生物学家和细胞生物学家，此外，上皮细胞的发育不正常是多种出生缺陷的原因，我们的工作可能会产生洞察力，在这种疾病的过程是有缺陷的。