Pattern Formation and the Regulation of Morphogenesis During Drosophila Oogenesis

University Of Washington, Seattle WA

Investigators

Abstract

Pattern Formation and the Regulation of morphogensis during Drosophila Oogenesis Unraveling the process by which multi-cellular organisms develop remains one of the major challenges in biology today. The studies proposed here examine the mechanism by which cells interpret positional information and coordinate cell migrations to generate shape and structure. Previous studies by other investigators in the field have focused mainly on the mechanics of cell movement, and most thoroughly in a few non-genetic systems such as frog development or tissue culture cell models. The work planned here focuses instead on the genetic regulatory hierarchies and cell signaling events that govern these cell biological forces. The proposed research uses the fruit fly Drosophila melanogaster as a model system to understand how cells coordinate their movements during development. Specifically, the work examines cell-cell interactions that direct the migrations of the follicle cells, the somatic cells that surround the oocyte, during their synthesis of two dorsal eggshell appendages required for respiration in the developing embryo. The advantages of this system pertain to the relatively simple nature of the tissue, the excellent culturing and imaging capabilities, and the outstanding genetic tools. The objectives of this research are threefold. (1) Determine the precise movements of the follicle cells using time-lapse confocal microscopy on cultured egg chambers. This analysis will assess the extent to which cell rearrangements and cell shape changes contribute to each phase of dorsal appendage synthesis. In addition, this approach will establish the relationship between a cell's fate, as determined by gene expressionmarkers, and its subsequent migratory behavior. (2) Investigate how cells coordinate their movements by studying cell behaviors in mutants that exhibit aberrant eggshell structures. Patterning mutants will be used to disrupt cell fate in subsets of migrating cells, then ask how neighboring cells respond. In addition, the overall migratory behavior of cells will be assayed in morphogenesis mutants with defects at specific stages of dorsal appendage formation. Both approaches will provide insight into the cell-cell interaction, cell adhesion, and cytoskeletal properties that control cell movements. (3) Examine the molecules that induce the cell movements and cell shape changes required for dorsal appendage formation. The PI will use the sophisticated genetic tools available in Drosophila to disrupt signaling and cell adhesion molecules that have been implicated in regulating the initial phases of dorsal follicle cell migration. These studies will establish the conserved nature of thedevelopmental process, not only at the morphogenetic level but at the molecular level as well. The overall goal of the proposed research is to understand how populations of cells coordinate their movement to generate the complex shapes required to make a functional tissue or organ. The pattern forming and morphogenetic events studied here represent the kinds of processes that take place during all stages of animal development, from the lowly fruit fly to the complex human. The ease of genetic, molecular, and cell biological approaches makes this system ideal for characterizing the processes by which cells transmit, receive and interpret positional information and thereby direct the ordered process of development