PGC PROLIFERATION · Somatic control of primordial germ cell proliferation

Control of cell proliferation is important during normal growth and, when impaired, might cause malignant transformation. While cell-autonomous control of proliferation has been studied extensively, cell proliferation in the context of a growing organ, when different populations of cells have to coordinate their growth is less well understood. We are using the ovary of the fruit fly Drosophila melanogaster as a model system for understanding how cell proliferation is controlled at the level of the developing organ. The ovary of Drosophila forms during embryogenesis. At the larval stages the somatic cells of the ovary proliferate and differentiate. The somatic niches for germ line stem cells (GSCs) form at that stage. Primordial germ cells (PGCs) also proliferate, and once the somatic niches form, a subset of PGCs become the adult GSCs. Control of PGC proliferation is therefore one of the factors that determine the number of GSCs that the organ will contain. We have performed a screen aimed at finding how PGC proliferation is controlled. Such a screen has not been attempted previously and was therefore likely to reveal novel regulators of cell proliferation. The screen uncovered both cell-autonomous and non-cell autonomous regulators of PGC proliferation. Some of the genes are known cell cycle regulators. Others are homologues of known human tumor-suppressors or oncogenes, which were never studied in the fly. Some of the genes were never shown to control cell proliferation. We propose to study the developmental role of the genes uncovered by the screen. To do so, we will first form a priority list of genes to study according to pre-determined criteria. Our highest priority genes will be those that act from somatic cells to control PGC proliferation. Our studies will provide a better appreciation of how PGC proliferation is controlled by neighboring cells, and how an organ might control the number of adult stem cells it contains.