Meiotic cell cycle progression in hermaphrodites and males is dependent on a germline signaling module comprising
let-60 RAS,
lin-45 RAF,
mek-2 MAPKK, and
mpk-1 MAPK. Strong lf alleles of these loci cause germ nuclei to arrest in pachytene, suggesting that the
let-60/mpk-1 cascade functions to transduce a signal necessary for the transition from pachytene to diplotene/diakinesis (Church et al. 1994). We are using three approaches to investigate this model. 1) By immunofluorescence, we find that the nuclei of presumptive oocytes begin to accumulate high levels of MAPK (or a cross-reacting antigen) just prior to the time of exit from pachytene. By analogy to MAPK behavior in vertebrate tissues, the nuclear translocation we observe may reflect MAPK activation. 2) In screens for sterile mutants, we have identified six pex genes (for defective in pachytene-exit). Among these loci, 5 have pachytene-arrest phenotypes very similar to known signaling mutants; 3 [
pex-1,
pex-3, & pex
(oz145) V] appear defective only in germline development; and 3 [
pex-2/let-21, pex
(oz209)V, & pex
(oz215) IV] also exhibit somatic defects. Three tested pex genes appear to act upstream of (or in parallel with) MAPK, as mutants fail to show nuclear translocation of germline MAPK. 3) Epistasis tests have revealed an interaction of
mek-2 and
mpk-1 with
gld-1. A
gld-1(null) mutation causes female germ cells to inappropriately exit pachytene and return to mitosis, but this phenotype is partially suppressed in a
mek-2(lf) or
mpk-1(lf) background. This suggests that MAPKK/MAPK activity promotes pachytene exit in the
gld-1(null) germ line and raises the possibility that
gld-1(+) has a role in negatively regulating pachytene exit. As the
gld-1(null) phenotype is not visibly suppressed by a strong
let-60(lf) RAS allele, we infer that
gld-1 may negatively regulate an effector that acts somewhere between
let-60 and
mek-2 to activate the kinase cascade that controls pachytene exit. We thank Mark Lackner and Stuart Kim for
mpk-1 alleles. Supported by NIH grants GM49785 (to E.L) and HD25614 (to T.S.).