The germline is a polar tissue with distal cells proliferating and more proximal cells initiating meiosis. The DTC - GLP-1/Notch receptor signaling pathway (1) promotes proliferation of distal germ cells by negatively regulating two redundant parallel pathways, one containing GLD-1 and the other GLD-2, that each promote initiation of meiosis (2,3). Germ cells in
gld-1 and
gld-2 single mutants enter meiosis normally, but fail to do so in the double mutant resulting in tumorous germlines analogous to constitutive activation of GLP-1 (3,4). Two screens were conducted to identify other genes necessary for entry into meiosis. First, three genes,
teg-1, -2 & -4 , where identified as recessive tumorous enhancers of a weakly activated
glp-1 allele. TEG-2 & -4 likely are negative regulators of GLP-1/Notch receptor signaling in both the germline and soma as
teg-2 & -4 mutations, but not
teg-1 , enhance the Muv phenotype of a weakly activating mutation in a second Notch receptor,
lin-12 . TEG-1 functions in the GLD-1 pathway to initiate meiosis as
teg-1 single mutant germ cells enter meiosis normally while the
gld-2;
teg-1 double mutant has a synthetic tumorous phenotype. In contrast, the
gld-1;
teg-1 double shows the
gld-1 null phenotype. Second, to identify genes acting in the GLD-1 pathway for entry into meiosis, recessive mutations that are synthetic tumorous in a
gld-2 background were isolated. This screen yielded
gld-1 mutations, a
teg-1 mutation and mutations in at least three other loci which have a synthetic tumorous phenotype with
gld-2 in both hermaphrodite and male germlines.
teg-1 also functions in the hermaphrodite germline sex determination pathway;
teg-1 promotes the female fate while
gld-1 and
fog-2 promote the male fate.
teg-1 negatively regulates
gld-1 and
fog-2 as both are epistatic to the
teg-1 masculinization of the germline (Mog) phenotype.
teg-1 is thus distinct from
mog-1 to -6 genes that act downstream of
gld-1 and
fog-2 in sex determination. Furthermore, sex determination genes downstream of
gld-1/fog-2 do not appear to be involved in the decision to initiate meiosis as none of the tested gene mutations show a synthetic tumorous phenotype with
gld-2 or suppress
gld-1;
gld-2 . 1) Kimble & Simpson '97; 2) Francis et al '95; 3) Kadyk & Kimble '98; 4) Berry et al '97