How do migrating epithelia change direction?

University Of Nevada Las Vegas, Las Vegas NV

Investigators

Abstract

LAY ABSTRACT: Animals build and maintain functional organs throughout their lives. To build an organ, multiple steps occur as the embryo develops, both to make all the different types of cells needed for that organ, and to organize these different cells so that they can work together to perform the organ's function. A common strategy for organizing cells is through coordinated cellular movements and shape changes. This project aims to understand how each different kind of cell obtains the information it needs to move into the correct places and acquire the needed shape. This process requires that cells recognize each other, assess their current location in the developing tissue, and finally, use information from their environment and/or in their DNA blueprint to navigate through the tissue to the location where they are needed. To understand how cells manage this intricate dance, the investigator will study an example where cells organize to create an organlike structure that develops into a fruit fly egg. A series of precise cellular movements is needed to build the eggshell, which protects the developing embryo. Fly ovaries will be cultured and cell movements will be imaged through the microscope, using genetic and antibody assays to identify the specific proteins that cells use to interact with each other. These studies will be able to distinguish whether the major source of information for a cell's movements come from an internal program or from external environmental cues. The proteins and mechanisms identified will expand the knowledge of the cellular repertoire available to create organized structure in the many different types of organs observed across animal phyla. This research will provide essential scientific training for undergraduate and graduate students at the University of Nevada, Las Vegas. They will acquire important skills in teamwork, critical thinking, data management,as well as the needed skills to perform laboratory research. TECHNICAL ABSTRACT: The experiments of this proposal will examine the mechanisms by which a migrating sheet of cells can change its direction of migration. The work will focus on oogenesis of the fruit fly Drosophila melanogaster, to take advantage of sophisticated tools for genetic manipulations and new technologies for real-time, time-lapse imaging of cellular movements in ovary explants. Based on previous research, two models for the mechanisms that induce the change in direction will be contrasted; these models are not mutually exclusive. One model is that each cell decides independently to change its direction, through an intrinsic program of regulated gene expression in response to a bone morphogenetic protein (BMP) morphogen gradient. Experiments will test specific candidate transcriptional regulators for their requirements in the onset of specific phases of the new migration. The second model is that the cells respond to an extrinsic signal that reorients their direction or otherwise changes their migration behavior. This aspect of the project follows up on published reports that the BMP response system may use non-transcriptional mechanisms to induce changes in cell shape, as well as preliminary data that another signaling system is modulated in these cells. The investigator predicts that intrinsic gene regulation initiates the competence for a migration response, and that extrinsic signals orient the cells' migratory behaviors. This work will identify the molecular links between developmental gene regulatory networks and the cellular effectors that create the diverse array of functional architecture seen in tissues of multicellular organisms. In addition to these research activities, the investigator is collaboratively organizing a monthly Science Cafe (www.sciencecafes.org) to provide an interactive venue for local and regional scientists to discuss current scientific topics with the general Las Vegas community.