This is a proposal to study how the dorsal air sacs of Drosophila adult develop. The dorsal air sacs are the major tracheal organs of the adult fly. They are complex, multi-lobed structures that function to fulfill the extreme demands of the indirect flight muscles for oxygen. Previous work in the Kornberg laboratory showed that dorsal air sac development begins during the third larval instar when a small group of cells in the wing imaginal disc produce FGF and this signaling protein induces nearby tracheal cells to embark on a program of growth and tubulogenesis. Their work also showed that long, cytoneme-like filopodia extend from the tracheal cells to the wing disc cells and that these cell extensions may serve as conduits for the movement of FGF between disc and tracheal cells. The studies proposed in this application delve further into the genesis of the dorsal air sacs, exploring how the cells of the wing disc and tracheal system interact to control the cell divisions, movements and growth during development of the dorsal air sacs.
Key issues addressed by this work are: 1) Experiments are proposed that will test the possibility that the progenitor cells of the dorsal air sac are the products of a developmental program that replaces larval tracheal cells with imaginal tracheoblasts during the third instar. Preliminary data obtained in the Kornberg lab suggests that this program involves regulated cell proliferation, death and migration and that it is triggered locally by the molting hormone ecdysone. Surprisingly, the tracheal cells themselves may synthesize the ecdysone that initiates this program. The role of ecdysone in regulating this program will be examined. 2) The genesis of most tubular organs in vertebrates involves extensive cell proliferation, but most tubular organs in Drosophila develop without cell proliferation. The dorsal air sacs are an exception, and experiments are proposed that will provide a better understanding of how cell proliferation is regulated and how it contributes to air sac development. 3) Secreted proteins provide instructional signals during development, but we do not yet understand how they move over long distances to reach their target cells. The interactions between the wing disc and tracheae that regulate dorsal air sac development present an excellent system to study the mechanism of long distance signaling. The structures that are postulated to mediate signaling will be examined.
The proposed activities will be carried out as part of a training program for graduate students and postdoctoral fellows at the University of California, San Francisco and will include the participation of undergraduate students recruited to UCSF through their Summer Research Training Program that provides undergraduates, including under-represented minorities, with opportunities to conduct research.
