In adult tissues, the tight regulation of stem cell self-renewal and differentiation maintains tissue homeostasis. In Drosophila ovaries, BMP signalling from the local environment maintains germline stem cells (GSCs) by repressing bam (a differentiation-promoting gene) expression. Now, on , Rongwen Xi and co-workers reveal a role for the tumour suppressor tuberous sclerosis complex proteins, TSC1/2, in GSC maintenance. Human TSC1 and TSC2 proteins form a complex that negatively regulates TOR, a conserved kinase involved in cell growth. TOR functions mainly via the TORC1 complex, which activates the protein translation initiator S6K. Disruption of Tsc1 or Tsc2 in Drosophila GSCs, the researchers report, leads to precocious GSC differentiation and loss. Elimination of S6K rescues this phenotype, which implicates TORC1 hyperactivation in the precocious differentiation of Tsc1/2 mutant GSCs. TORC1 hyperactivation also negatively regulates BMP signalling. Thus, suggest the researchers, TSC1/2-TORC1 signalling maintains Drosophila GSCs by controlling both BMP-Bam-dependent and -independent differentiation programs, a role that might be conserved in mammals.
