Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture Epithelial sheets sit at the boundary of the organism and its external environment. The maintenance of these apical and basolateral domains is essential to the barrier function of epithelia, and the loss of apical-basal polarity is associated with the metastasis of many epithelial cancers. While epithelial sheets were once viewed as largely static assemblies, it is now appreciated that these are dynamic structures that can undergo significant reorganizing and renewal events. Indeed, cell neighbor exchange can be harnessed by developmental processes to effect changes in tissue architecture, and cell intercalation can drive epithelial tissue repair. In the Drosophila embryonic epithelium, individual cells are able to either consolidate cell-cell contacts or direct neighbor exchange movements through the asymmetric localization of cell adhesion and polarity proteins. While it is now apparent that actomyosin contraction drives the shrinking and loss of cell-cell interfaces, the means by which epithelial cells create new cell contacts and interfaces is unknown. The main question addressed in this project is the identification of the mechanism by which new cellular interfaces are established and maintained. We hypothesize that an early and essential event in the creation of the new interfaces that drive neighbor exchange will be directed membrane addition. The role of a key mediator of new membrane addition, the exocyst complex, in directing localized vesicular trafficking during tissue elongation will be characterized. We will also generate novel tools by drawing on recently created optical highlighter proteins that will allow the dynamic tracking of specific subpopulations of adhesion proteins. These tools and techniques should be useful to the general Drosophila community. Finally, genetic approaches are underway to identify new components involved in the establishment of distinct properties of cell polarity. The approaches used in these studies will draw on advanced imaging techniques that are just beginning to be applied to Drosophila. The funding of this project will be the first major grant for the newly established lab and will represent an important step towards the founding of an independent research program.
Epithelial tissues, such as the human skin and gut, maintain an essential polarity that allows the cells in these tissues to confront both the external environment of the organism and the aqueous internal environment. The maintenance of this polarity is essential to the barrier function of epithelia, and the loss of this polarity is associated with the metastasis of many epithelial cancers. The intention of this proposed study is to examine the processes that direct epithelial cell adhesion, thus leading to a better understanding of how the critical tissue integrity of epithelial tissues is maintained and can be disrupted by disease.
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