Mechanisms of epithelial morphogenesis in drosophila

我的研究项目的目的是了解随着有机体的发育，具有不同形式和功能的结构是如何产生的。例如，随着单个细胞改变形状或经历不同的运动，最初统一的细胞片或上皮可以呈现复杂的形式。我们使用果蝇的卵巢作为一个简单的实验系统，来了解细胞内的哪些分子执行这些细胞行为。卵巢的滤泡上皮包围着每个发育中的卵子，一开始是统一的片状，但随着时间的推移，组织中的两组细胞经历了一系列形状变化。在组织中产生折叠，然后形成两管细胞，这些细胞从平板上投射出来。我们已经识别出一种名为棘球蛋白(Ed)的基因，它似乎通过协调最初产生折叠的细胞形状的变化来帮助产生这些管。ED蛋白的结构表明，它通常位于细胞表面，我们的工作表明，ED帮助细胞识别并相互作用。有趣的是，当有ED的细胞与没有ED的细胞相邻时，细胞骨架的变化导致并驱动细胞形状的变化，从而完成管的形成。我们现在将确定有和没有ED的细胞之间的界面是如何导致这种现象的，以及ED与哪些分子相互作用才能产生这种细胞行为。除了我们对ED的研究外，我们正在开发一种新的技术来识别其他在塑造组织中起作用的基因。找到新的相关基因将增强我们对这些过程如何工作的理解。我们在这个简单系统中的发现将增加我们对在人类中观察到的类似细胞过程的了解，在人类中，上皮细胞经历类似的运动来产生肾小管网络，肺和乳腺。在伤口愈合过程中也观察到了这些细胞行为。由于大多数果蝇基因都有人类的等价物，深入了解控制细胞如何相互作用的基因，以及这些相互作用如何塑造组织，将进一步加深我们对人类正常和异常发育的理解。

The aim of my research program is to understand how structures with different form and function arise as an organism develops.  For example, an initially uniform sheet of cells, or epithelium, can take on a complex form as its individual cells change their shapes or undergo various movements.  We use the ovary of the fruit fly, Drosophila melanogaster, as a simple experimental system for understanding what molecules inside the cell carry out these cellular behaviors.  The follicular epithelium of the ovary, which surrounds each developing egg, starts out as a uniform sheet but, over time, two groups of cells in the tissue undergo a series of shape changes, creating folds in the tissue that go on to form two tubes of cells that project from the flat sheet.     We have identified a gene, named echinoid (ed), that appears to help generate these tubes by coordinating the cell shape changes that first create the folds.  The structure of the Ed protein suggests that it is normally located on the surface of cells and our work suggests that Ed helps cells recognize and interact with each other.  Interestingly, when cells with Ed are adjacent to cells without Ed, changes in the skeleton of the cell result and drive the changes in cell shape that complete tube formation.  We will now determine how the interface between cells with and without Ed causes this phenomenon, and which molecules Ed interacts with to generate this cellular behaviour.  In addition to our studies of Ed, we are developing a new technique for identifying other genes that function in shaping tissues.  Finding new genes involved will enhance our understanding of how these processes work.   Our findings in this simple system will increase our knowledge of similar cellular processes are observed in humans, where epithelia undergo similar movements to generate the tubular networks of the kidney, lung and mammary gland.  These cellular behaviors are also observed in wound healing.  Since most Drosophila genes have human equivalents, insight into the genes that control how cell interact with each other, and how these interactions shape tissues, will further our understanding of both normal and abnormal human development.