CASANUEVA, M. O.; FERGUSON, E.; Univ. of Chicago: Germline stem cell (GSC) number in the Drosophila ovary is regulated by redundant mechanisms that control the perdurance of Decapentaplegic (Dpp) signaling.

GSCs of the Drosophila ovary undergo an asymmetric self-renewal division that gives rise to a GSC and a Cystoblast (Cb), one of whose daughters will become an oocyte. The current model is that that GSCs are present in an environmental niche within the anterior-most germarium and that Dpp, a member of the TGF-beta family of ligands, acts as a niche signal that maintains GSCs. Conversely, it has been shown that Bag of marbles (Bam), which encodes a novel protein, is both necessary and sufficient to promote the differentiation of Cbs. The prevalent model is the Dpp locally signals to repress the expression of Bam within the GSCs. We have observed that one known Dpp target gene, Daughters against Dpp (Dad), is expressed in somatic cells that span far beyond the anterior niche. Nevertheless, within the germline, Dad is solely expressed in GSCs and in Cbs, suggesting that the very restricted extent of Dpp signaling within the germ line is not determined only by local distribution of ligand, but rather may be actively controlled by mechanisms intrinsic to the germ line. In a series of genetic experiments we have identified two functionally redundant mechanisms that act in the germ line to downregulate Dpp signaling. One such mechanism includes the function of Bam, that acts in a negative feedback fashion to block Dpp signaling. The second mechanism involves a ubiquitin protein-ligase, D-smurf, which likely functions to ensure activated Dpp receptor turnover. These results raise the possibility that Dpp signaling plays an instructive role for GSC maintenance and that it must be downregulated in order for Cb differentiation to occur.