In order to identify gene products that are Fovided matemally and required for normal germ-line development, we have been screening for grandchildless mut.nions. One of the loci we have identified,
mes-3, appears to be a good candidate for such a gene product. Homozygous mutant offspring of heterozygous
mes-3/+ mothers are themselves fertile, but produce all sterile progeny. Three lines of evidence suggest that mutations at this locus primarily affect the germ line. First, temperature-shift experiments and parental-effect tests suggest that the
mes-3 gene product acts early during embryogenesis. Second,
mes-3 mutant animals show no other obvious defect besides maternal- effect sterility. Finally, alleles are being isolated at a frequency consistent with loss-of-function mutations. In addition,
mes-3/Df animals show a phenotype identical to
mes-3 homozygous mutant animals, suggesting that the grandchildless phenotype is the null phenotype. Progeny of
mes-3 mutant animals are sterile due to abnormal germ- line proliferation during larval development. Ll larvae from
mes-3 mothers hatch with apparently normal germ-line precursor cells. These begin to divide at the apFopriate stage, but never reach wild-type proliferation levels.
mes-3 sterile adult hermaphrodites show 10- to 100-fold reductions in numbers of germ-line nuclei and do not produce gametes. Surprisingly,
mes-3 male offspring are less severely affected, showing only 3- to 6-fold reductions in numbers of germ nuclei. Some of these animals produce sperm and a fraction of these produce viable progeny. At this point, it is unclear whether the
mes-3 proliferation defect is due to incorrect specification of germ cell fate or to a specific effect on germ-line proliferation. One possibility is that mutations at the
mes-3 locus may perturb the ability of germ nuclei to respond to the proliferation signal of the distal tip cell. Some support for this idea comes from the observation that in
mes-3 mutant Fogeny, the male germ line, which is responding to the signal of two distal tip cells, proliferates to a greater extent than the hemaphrodite germ line. In addition, preliminary genetic evidence suggests that a glp-l mutation enhances the proliferation defect of one of the
mes-3 alleles. In conclusion, it appears that maternal expression of the
mes-3 gene product is required for normal germ-line development. The locus maps between
unc-38 and dpv-S on chromosome I. We are attempting to clone the gene in order to shed some light on when and how it affects formation of the germ line.