GLP-1 is a Notch-type receptor that mediates a proliferative signal from the somatic distal tip cells to the germ line. In the absence of GLP-1 signaling, germ cells exit mitosis, enter meiosis, and differentiate. A single allele of
ego-2,
om33, was identified in screens for recessive enhancers of
glp-1(ts) in the germ line and mapped between
dpy-24 and
unc-75 on chromosome I (Qiao et al., 1995). Analysis of
ego-2 was confounded by the presence of linked mutations, including a ts
fer-6 allele. Recently, we recombined off the flanking mutations and characterized the
ego-2(
om33) phenotype.
ego-2(
om33) causes a ts germline proliferation defect. At 25C, the
ego-2(
om33ts) germline "mitotic zone" is lost at a variable point during larval development or early adulthood. At 20C, the
ego-2(
om33ts) mitotic zone persists well into adulthood but is often lost in older adults. Germ cells can enter and proceed through meiosis. This late-onset loss of germ cell proliferation resembles the phenotype of a weak
glp-1 mutation. At 20C,
ego-2(
om33);
glp-1(
bn18ts) animals typically have a severe Glp-1 germ line. The mitotic zone is typically lost in early larval development and all germ cells enter meiosis and form gametes. The phenotype is variable; the occasional animal has a much larger germ line and makes oocytes. In addition to its role in the germ line, GLP-1 mediates several inductive events in the embryo; this
glp-1 activity is maternally provided. We find that
ego-2(ts) enhances the
glp-1 maternal effect lethality.
ego-2 was previously mapped to the right of
dpy-24 (Qiao et al., 1995). We have since obtained data that shuffle the position of
dpy-24 relative to other genes in the vicinity. In addition,
aph-2/Nicastrin was identified as a component of at least some Notch-type signaling events in C. elegans and mapped to the vicinity of
ego-2 (Goutte et al., 2000; Levitan et al., 2001). We find that both
ego-2(
om33)/aph-2(null);
glp-1(
bn18ts) and
aph-2(null);
glp-1(
bn18ts) animals have an enhanced Glp-1 phenotype. However,
ego-2/aph-2 transheterozygotes are enhanced to a lesser degree than either
ego-2 or
aph-2 homozygotes. DNA sequencing failed to detect a mutation in the
aph-2 gene isolated from the
ego-2(
om33ts) strain. Therefore,
ego-2 seems to be an independent gene and encode an additional component of the GLP-1-mediated signaling pathway.
aph-1 maps to the left of the
ego-2 region, however it functions in GLP-1-mediated signaling and interacts with
aph-2 (Goutte et al., 2002). For completeness, we also sequenced the
aph-1 gene from our
ego-2 strain; no mutation was found. We are currently using SNP mapping to localize
ego-2.