1. Howard Hughes Medical Institute, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA
2. Department of Biochemistry, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA
3. Program in Cellular and Molecular Biology, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA
4. Program in Molecular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
5. Present addresses: Department of Anatomy, The University of California, San Francisco, California 94143, USA (M.G.); Wormbase, Caltech 156-29, Pasadena, California 91125, USA (A.G.P.)

Correspondence to: Judith Kimble^1,2 Correspondence and requests for materials should be addressed to J.K. (e-mail: Email: jekimble@facstaff.wisc.edu).

Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes¹. The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell^{2, 3}. FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF ('fem-3 mRNA binding factor'), were originally discovered as regulators of germline sex determination⁴. Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle^{5, 6}. FBF belongs to the PUF family ('Pumilio and FBF') of RNA-binding proteins⁷. Pumilio controls germline stem cells in Drosophila females^{8, 9}, and, in lower eukaryotes, PUF proteins promote continued mitoses^{10, 11}. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.