The PIE-1 protein is localized to cells of the germ lineage in the early C. elegans embryo where it functions to suppress somatic cell fates. We have found that mutant strains in which PIE-1 protein is mislocalized to somatic cells exhibit a sterile phenotype, but in most cases undergo fairly normal somatic differentiation. These observations suggest that while the threshold for PIE-1 function in suppressing somatic development is set high, slight reductions in PIE-1 levels may be sufficient to prevent germline protection leading to sterility. This may explain why certain PIE-1 genetic backgrounds as well as strains defective in functions required for PIE-1 localization appear to exhibit haplo-insufficient dominant sterile phenotypes (See Shin, et al). These observations led us to initiate screens for Dominant Maternal Effect Sterile mutations (DMES). Steriles are a very common phenotypic class. In standard genetic screens dominant maternal effect steriles will arise in the F2 among a huge background of recessive zygotic steriles. To avoid this difficulty we decided to ask if the diploid oocytes within the proximal arms of a mutagenized animal might be considered as independent mothers. If so then this would permit us to screen for dominant maternal effects among the F1 progeny of a mutagenized animal. We know from our previous dealings with pie-1 associated sterility that affected animals can often produce a few fertile viable offspring so we screened in an egg-laying defective background for F1 animals with only a few embryos developing inside. We first did a pilot screen of 30,000 F1 mutagenized animals. From this screen we obtained two mutations that behave like bona fide DMES loci, and a few that appear to be zygotic effect Dominants. One of the DMES mutants (ne146) , exhibits mislocalization of both the PIE-1 protein and of the P-granules. This mutation fails to complement previously identified maternal effect lethal alleles of the par-2 locus. The second DMES mutation mapped genetically to the location of a gene, alp-1 that encodes a PIE-1 binding protein, and indeed our mutant allele appears to contain a point mutation in this gene (See Shin et al.). This initial success has encouraged more screens which are presently underway.

Affiliation:
- Cancer Center, UMMC Worcester, MA 01605