Regulation of cell-cell recognition during epithelial development

上皮组织是由组织成连续薄片的细胞组成的，这种组织由组成细胞之间的物理相互作用来维持。我的研究重点是了解上皮组织的发育，特别是相邻细胞之间相互作用的调节如何驱动表征组织发育的上皮组织和功能的变化。 这项工作以果蝇卵巢的卵泡上皮为模型，研究了决定组织特性的细胞-细胞相互作用的分子基础，并探讨了它们在组织发育过程中的调节如何导致其形态和功能的重要变化。这项工作的一个重点是嗜同型细胞黏附分子棘球蛋白(Echinid)，我们先前已经证明它在这种上皮的形态发生中起着重要的作用。ED在该组织中表现出时间和空间上的动态表达模式，在这里，我们建议识别ED表达的上游调控因子。我们还注意到，ED的这种丧失与卵黄在发育中的卵母细胞中的摄取是一致的，这一过程涉及到卵黄蛋白从循环血淋巴中转移到卵泡上皮。在许多昆虫中，这种运动包括毛囊细胞之间短暂出现的细胞间隙，使卵黄蛋白得以通过。我们有兴趣了解该系统中卵黄通过的等效机制，并询问是否需要失去ED。 目的1：探讨卵子发生过程中ED基因表达的调控水平。 目的2：检测卵子发生中期ED表达缺失的候选上游调控因子。 目的：研究卵子发生中期卵黄穿过卵泡上皮的过程，并验证ED丢失参与此过程的假说。 长期目标：a)应用目标1和2中的方法和见解来研究胚胎中ED的调节，以及b)确定卵黄蛋白在卵子发生中期通过卵泡上皮所涉及的其他因素。 结果：这项工作很重要，因为它使用一个具有良好特性的模型系统，以及体内遗传操作的各种工具，研究细胞-细胞相互作用的调节如何调节发育重要的上皮属性。这将有助于我们理解ED，它是已知的介导细胞间相互作用的物质，以及允许重要分子跨越上皮屏障的调节机制这一基本问题。这项工作将为HQP培训做出贡献，为学员提供分子生物学、组织学和先进成像技术方面的直接技术专业知识，并提供沟通和批判性思维技能，使他们为各种职业道路做好准备。

Epithelial tissues are composed of cells that are organized into continuous sheets, and this organization is maintained by physical interactions between the component cells. My research program focuses on understanding the development of epithelial tissues, in particular how the regulation of the interactions between neighboring cells can drive the changes in epithelial organization and function that characterize the development of the tissue. Using the follicular epithelium of the Drosophila ovary as a model, this work investigates the molecular basis for the cell-cell interactions that determine the properties of the tissue and asks how their regulation during the development of the tissue leads to important changes in its form and function. One focus of this work is the homophilic cell adhesion molecule Echinoid (Ed), which we showed previously plays an important role in morphogenesis of this epithelium. Ed displays a temporally and spatially dynamic expression pattern in this tissue, and here we propose to identify the upstream regulators of Ed expression. We also noted that this loss of Ed coincides with the uptake of yolk in the developing oocyte, a process that involves transit of yolk proteins from the circulating hemolymph across the follicular epithelium. In many insects, this movement involves the transient appearance of intercellular spaces between follicle cells that allow the passage of yolk proteins. We are interested in understanding the equivalent mechanism for yolk passage in this system, and asking whether it requires loss of Ed. Aim 1: To determine at what level Ed expression is regulated during oogenesis. Aim 2: To test candidate upstream regulators of the loss of Ed expression during mid-oogenesis. Aim 3: To characterize the passage of yolk across the follicular epithelium during mid-oogenesis and test the hypothesis that loss of Ed is involved in this process. Long term goals: a) to apply the approaches and insights from Aims 1 and 2 to investigate regulation of Ed in the embryo, and b) to identify additional factors involved in passage of yolk proteins through the follicular epithelium in mid-oogenesis. Outcomes: This work is important because it investigates, using a well-characterized model system with a variety of tools for in vivo genetic manipulation, how the modulation of cell-cell interactions regulates developmentally important epithelial properties. It will contribute to our understanding of Ed, which is known to mediate intercellular interactions, and to the fundamental question of the regulatory mechanisms that allow transit of important molecules across epithelial barriers. This work will contribute to HQP training by providing trainees with direct technical expertise in molecular biology, histology and advanced imaging techniques, and also with the communication and critical thinking skills that will prepare them for a variety of career paths.