RNA-binding proteins control germline development in metazoans. This work focuses on control of the C elegans germline by two RNA-binding proteins: FOG-1, a CPEB homolog; and FBF, a PUF family member. Previous studies have shown that FOG-1 specifies the sperm fate and that FBF promotes proliferation. Here, we report that FOG-1 also promotes proliferation. Whereas
fbf-1 Jbf-2 double mutants make similar to 120 germ cells,
fog-1;
fbf-1 Jbf-2 triple mutants make only similar to 10 germ cells. The triple mutant germline divides normally until early L2, when germ cells prematurely enter meiosis and begin oogenesis. Importantly,
fog-1/+;
fbf-1 fbf-2 animals make more germ cells than
fbf-1 fbf-2 double mutants, demonstrating that one dose of wild-type
fog-1 promotes proliferation more effectively than two doses - at least in the absence of FBF. FOG-1 protein is barely detectable in proliferating germ cells, but abundant in germ cells destined for spermatogenesis. Based on
fog-1 dose effects, together with the gradient of FOG-1 protein abundance, we suggest that low FOG-1 promotes proliferation and high FOG-1 specifies spermatogenesis. FBF binds specifically to regulatory elements in the
fog-1 3''''UTR, and FOG-1 increases in animals lacking FBF. Therefore, FBF represses
fog-1 expression. We suggest that FBF promotes continued proliferation, at least in part, by maintaining FOG-1 at a low level appropriate for proliferation. The dose-dependent control of proliferation and cell fate by FOG-1 has striking parallels with Xenopus CPEB, suggesting a conserved mechanism in