Mechanisms of epithelial morphogenesis in drosophila

我的研究计划的目的是了解不同形式和功能的结构是如何随着生物体的发展而出现的。例如，最初均匀的细胞片或上皮，随着单个细胞改变形状或经历各种运动，可以呈现复杂的形式。我们用果蝇（Drosophila melanogaster）的卵巢作为一个简单的实验系统，来了解是什么分子在细胞内执行这些细胞行为。卵巢的卵泡上皮，包围着每个正在发育的卵子，开始时是一个均匀的薄片，但随着时间的推移，组织中的两组细胞经历了一系列的形状变化，在组织中产生褶皱，形成两个从扁平薄片伸出的细胞管。我们已经确定了一种名为棘轮样蛋白（ed）的基因，它似乎通过协调细胞形状的变化来帮助产生这些管，而细胞形状的变化首先会产生褶皱。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帮助细胞识别和相互作用。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Ed和没有Ed的细胞之间的界面是如何引起这种现象的，以及Ed与哪些分子相互作用以产生这种细胞行为。除了我们对Ed的研究，我们正在开发一种新技术来识别其他在组织塑造中起作用的基因。发现新的相关基因将增强我们对这些过程如何运作的理解。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认识，在人类中，上皮细胞经历类似的运动来产生肾、肺和乳腺的管状网络。这些细胞行为也在伤口愈合中被观察到。由于大多数果蝇的基因与人类的基因相同，因此深入了解控制细胞如何相互作用以及这些相互作用如何形成组织的基因，将进一步加深我们对正常和异常人类发育的理解。

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.