A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans

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Abstract
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 cell2,3. 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 cycle5,6. FBF belongs to the PUF family (‘Pumilio and FBF’) of RNA-binding proteins7. Pumilio controls germline stem cells in Drosophila females8,9, and, in lower eukaryotes, PUF proteins promote continued mitoses10,11. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.