Regulation of cell-cell recognition during epithelial development

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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.********