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

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 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.