Analyses of Germ Cell Migration and Programmed Cell Death in Drosophila melanogaster

Iowa State University, Ames IA

Investigators

Abstract

0235332 Coffman During animal development, many cells must migrate to their ultimate destinations in order to function. The regulatory mechanisms that control the elimination of cells that fail to migrate appropriately, present a danger to the animal, or that are in excess are often tightly linked to cell migration. However, the mechanisms that regulate how and where a cell moves and whether it lives or dies are not well understood. Germ cell development in the fruit fly, Drosophila melanogaster, is a genetically tractable system for studying cell migration and programmed cell death. Successful screens from other labs have identified zygotically required autosomal genes involved in germ cell migration. However, those genes identified to date have enigmatic functions, and the relationships between the various known components are not clear. Programmed death of Drosophila germ cells was proposed over 50 years ago, but the cellular and molecular mechanisms regulating this process are virtually unexplored. To identify additional genes required for germ cell development, a genetic screen of the X chromosome was performed. This proposal outlines studies of 2 genes that, when mutated, severely disrupt germ cell migration and/or cell death. When both the maternal and zygotic functions of scattershot (sctt) are disrupted, the germ cells form normally and initiate migratory movements, but very few, if any, reach the gonad. Germ cells ectopic to the gonad, which normally undergo cell death, fail to die. A paternal wild-type copy of sctt can rescue the migration defect, but not the cell death defect. The function of the outsiders (out) gene is required zygotically. In out mutant embryos, a wild-type number of germ cells migrate to the gonads, but many germ cells ectopic to the gonads fail to undergo programmed cell death. This project will: 1. Contribute to the emerging germ cell migration and cell death models by determining the molecular identity and characterizing the mRNA expression patterns of sctt and out. 2. Test the hypotheses that sctt and out functions are required in the germ cells. 3. Test specific hypotheses about interactions between sctt and out with previously identified cell migration or cell death components. 4. Educate undergraduate and graduate researchers from underrepresented groups. 5. Contribute to the understanding of the basic biological mechanisms regulating cell migration and cell death. This will lead to new hypotheses concerning the etiology of disease conditions including birth defects, autoimmune diseases, and cancer.