Regulation of cell-cell recognition during epithelial development

上皮组织由组织成连续片状的细胞组成，这种组织是通过组成细胞之间的物理相互作用来维持的。我的研究项目侧重于理解上皮组织的发育，特别是如何调节相邻细胞之间的相互作用，从而驱动上皮组织和功能的变化，这些变化是组织发育的特征。***本研究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式和功能的重要变化。这项工作的一个重点是亲同质细胞粘附分子Echinoid (Ed)，我们之前发现它在这种上皮的形态发生中起重要作用。Ed在该组织中表现出一种时间和空间动态的表达模式，在此我们建议确定Ed表达的上游调控因子。我们还注意到，Ed的丧失与卵黄在发育中的卵母细胞的摄取一致，这一过程涉及卵黄蛋白从循环血淋巴转运到卵泡上皮。在许多昆虫中，这种运动涉及卵泡细胞之间的细胞间隙的短暂出现，使卵黄蛋白得以通过。我们有兴趣了解该系统中卵黄传代的等效机制，并询问是否需要丢失Ed。***目的1：确定在卵子发生过程中，Ed的表达在什么水平上受到调节。***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3：表征卵黄在卵泡上皮发生中期的传递过程，并验证Ed缺失参与这一过程的假设。***长期目标：a)应用目标1和目标2的方法和见解来研究胚胎中Ed的调控，b)确定卵黄蛋白通过卵泡上皮在卵子发生中期传代的其他因素。***结果：这项工作很重要，因为它使用一个具有良好特征的模型系统和各种工具进行体内遗传操作，研究细胞-细胞相互作用的调节如何调节发育重要的上皮特性。这将有助于我们对Ed的理解，已知Ed介导细胞间相互作用，以及允许重要分子跨越上皮屏障的调节机制的基本问题。这项工作将有助于HQP培训，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长，以及为各种职业道路做好准备的沟通和批判性思维技能。********

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.********