Regulation of Stem Cell Maintenance and Transit Amplifying Cell Proliferation by TGF-β Signaling in Drosophila Spermatogenesis

The continuous and steady supply of transient cell types such as skin, blood and gut depends crucially on the controlled proliferation of stem cells and their transit amplifying progeny. Although it is thought that signaling to and from support cells might play a key role in these processes, few signals that might mediate this interaction have been identified. During spermatogenesis in Drosophila, the asymmetric division of each germ line stem cell results in its self-renewal and the production of a committed progenitor that undergoes four mitotic divisions before differentiating while remaining in intimate contact with somatic support cells [1]. Previous data have suggested that TGF-beta signaling pathway components punt and schnurri are required in the somatic support cells to restrict germ cell proliferation. Here, by contrast, we show that the maintenance and proliferation of germ line stem cells and their progeny depends upon their ability to transduce the activity of a somatically expressed TGF-beta ligand, the BMP5/8 ortholog Glass Bottom Boat. We further demonstrate that TGF-beta signaling represses the expression of the Bam protein, which is both necessary and sufficient for germ cell differentiation, thereby maintaining germ line stem cells and spermatogonia in their proliferative state.