Cell migration is a fascinating feature of embryonic development, and improperly regulated cell migration contributes to birth defects and tumor metastasis. We have developed a simple model system for a forward genetic approach to the study of cell migration in vivo, the movement of a subset of follicle cells, known as border cells, in the Drosophila ovary. We have established that at least three extracellular signals must impinge on the cells in order for them to move correctly. 1) The steroid hormone ecdysone, acting through the ecdysone receptor and a transcriptional coactivator called Taiman, is required. Since the ecdysone titer peaks specifically at the stage during which the border cells migrate, we propose that ecdysone could control the timing of border cell migration. 2) A highly localized cytokine signal, which activates the JAK/STAT pathway, is required to define the invasive population of cells and sustain their motility. 3) A growth factor referred to as PVF1 is involved in guiding the border cells to their destination. The focus of this proposal will be to characterize in further depth the precise functions of these signals and to identify additional signals that control when and where the cells migrate. Our first specific aim will be to test the hypothesis that ecdysone regulates the timing of border cell migration in conjunction with another signal and to identify the second signal.
Our second aim will be to test the hypothesis that the Taiman protein, which is a member of the p160 family of steroid hormone receptor coactivators, serves to integrate multiple signals. In particular we propose that Taiman may integrate ecdysone and juvenile hormone signals. In our third aim, we propose to identify additional guidance factors for border cell migration and to investigate the tissue-specificity of PVF1 and PVF2. In our fourth and final aim we will test the hypothesis that UPD secreted by the polar cells can only activate the JAK/STAT pathway to high levels in cells that are in physical contact with UPD expressing cells. We will also investigate the biochemical mechansims that tether UPD to the cell membrane. ? ? ?
Showing the most recent 10 out of 27 publications
