Cell migration is critical to normal development. Germ cell migration is a conserved process where germ cells formed in one region must travel through the developing embryo to reach their destination. I used germ cell migration in Drosophila melanogaster embryos as a model to functionally dissect migratory signaling pathways in vivo. In Drosophila the G protein coupled receptor Tre1 is essential for the initiation and active migration of germ cells to the somatic gonad.
My thesis research sought to uncover signaling pathways that act up and downstream of Tre1. I found that multiple genes including RhoGAP, rtGEF, lipid modifiers, and actin cytoskeletal components are required for Tre1 mediated signaling. Tre1 is a Rhodopsin-like GPCR that contains the highly conserved E/N/DRY and NPxxY motifs. In a structure-function approach, I uncovered overlapping and unique roles for these conserved domains in the initiation and subsequent migration of germ cells to the gonad. This work revealed a mechanism by which the Tre1 NPIIY domain is required specifically for polarization of downstream signaling components whereas the NRY domain is required for reading and responding to migration and survival cues mediated by the Drosophila lipid phosphate phosphatase, Wunen. My studies therefore suggest that the processes of cell polarization and directional migration are controlled by separate pathways downstream of Tre1.
The studies presented here reveal interesting insights into the molecular mechanism governing the initiation of germ cell migration in Drosophila. Furthermore, this work uncovers unique roles in GPCR biology and may provide new insight into directed cell migration in other systems.
|Commitee:||Baylies, Mary, Christiaen, Lionel, Nance, Jeremy, Treisman, Jessica|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 77/07(E), Dissertation Abstracts International|
|Subjects:||Genetics, Cellular biology, Developmental biology|
|Keywords:||Cell migration, GPCR, Germ cell, Tre1|
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