Germline fates are controlled, at least in part, by conserved RNA regulators. For the hermaphrodite sperm/oocyte switch, FBF, a Pumilio-related RNA-binding protein, represses the activity of
fem-3 mRNA and thereby promotes oogenesis (1). The Nanos homolog
nos-3 acts together with FBF to promote oogenesis (2), and GLD-3, a Bicaudal C-related KH-domain protein, antagonizes FBF to promote spermatogenesis (3). In addition to its role in sex determination, FBF also regulates germline stem cells: fbf mutant adults have no germline stem cells and make no oocytes (4). To promote mitosis, FBF represses the activity of
gld-1 mRNA. The
gld-1 gene regulates entry into meiosis as well as sex determination (5), and in both cases promotes the cell fate that FBF represses (4). Entry into meiosis is regulated by at least two parallel pathways. The two pathways are represented by
gld-1 and
gld-2, which are functionally redundant for entry into meiosis (6). We have found that
gld-3 and
nos-3 also play roles in entry into meiosis. Genetic evidence suggests that
gld-3 acts with
gld-2 in one branch of the pathway. Single
gld-2 and
gld-3 mutants have similar effects on the position of the mitosis/meiosis boundary, and each mutant can weakly suppress the fbf proliferation defect. In addition,
gld-3 is redundant with
gld-1, but not
gld-2, for entry into meiosis, indicating that
gld-2 and
gld-3 can act in the same branch of the pathway. This is consistent with molecular data that GLD-2 and GLD-3 act together as an atypical poly(A) polymerase (7) and exist in a complex in vivo. In contrast to
gld-2 and
gld-3,
nos-3 has no effect on the position of the mitosis/meiosis boundary and suppresses the fbf proliferation defect more strongly. In addition,
nos-3 is redundant with
gld-3 but not
gld-1 for entry into meiosis, indicating that it may act in the
gld-1 branch of the pathway. Yeast three hybrid and gel shift experiments suggest that
gld-3 mRNA is repressed by FBF. Thus, FBF represses at least one mRNA (
gld-1 and
gld-3) of each branch of the pathway, ensuring continued mitoses. 1. Zhang et al (1997) Nature 2. Kraemer et al (1999) Current Biology 3. Eckmann et al (2002) Developmental Cell 4. Crittenden et al (2002) Nature 5. Francis et al (1995) Genetics 6. Kadyk and Kimble (1998) Development 7. Wang et al (2002) Nature