The
par-5 gene is required maternally for the establishment of asymmetric cell divisions in early C. elegans embryos. Mutant embryos produced by homozygous
par-5 mothers typically develop into multicellular aggregates of differentiated cells. However, at 15 degrees C, 5-20% of the embryos hatch and develop into sterile adults. Sterility among these rare "leaky progeny" has been observed for other par mutants and was assumed to be associated with problems in P-granule segregation. However, our recent studies of
par-5 (
lw19) "leakers" reveal that many of these
par-5 sterile animals have gonadal defects characteristic of mutations in the ras/raf cell signaling pathway. Specifically, the gonads of the affected hermaphrodites contain disorganized and clumped patches of pachytene nuclei as has been previously described for
mek-2 and
let-60 (ras) mutants (Church et. al, 1995). These studies by Church and co-workers suggest that, in addition to vulval induction, the ras/raf cell signaling pathway regulates the transition between pachytene and diakinesis during oogenesis. This
let-60 (ras)-like phenotype of
lw19 animals is significant because
par-5 has recently been identified as a germline isoform of 14-3-3 (Shakes et al., this meeting). Dimers of 14-3-3 are thought to serve as molecular "matchmakers" which facilitate the interaction of specific proteins via two ligand binding sites. 14-3-3 binding proteins share a common six amino acid motif whose binding strength is regulated by serine phosphorylation (Muslin et al., 1996). The gonadal phenotype of
par-5 (
lw19) combined with the knowledge that Raf is a known 14-3-3 binding protein suggests that
par-5 (14-3-3) may help regulate the various cell cycle and cellularization events of the gonadal loop region. We are currently testing whether "leaky progeny" from other
par-5 alleles exhibit similar defects.