egl-38 mutations arose in screens for egg-laying defects, male spicule defects, and lethality. Genetic analysis indicates that the null phenotype of
egl-38 is lethal for both males and hermaphrodites. Lethality generally correlates with heavy damage, or "scarring," at the rectum. L1's die at hatching, often exploding at the rectum and immediately disintegrating. Better understanding of the basis for the lethal phenotype comes from lineage analysis of males bearing non-null mutations. In
egl-38 males, the cell lineages of the rectal epithelial cells F and U are disrupted. Specifically, the F and U cell progeny often divide prematurely, and in some cases the U cell divides with the timing and axes of Y.p. Thus
egl-38 is required to make U different from its posterior neighbor, Y, or possibly the daughter, Y.p. We speculate that F and U play an important role in maintaining the structural integrity of the rectum, and the lethal phenotype results from fate disruptions within the rectal epithelium. The Egl phenotype reflects cellular defects in development of both the hermaphrodite vulva and uterus. Although the vulva cell lineage is normal in
egl-38 mutants, the anchor cell is positioned abnormally relative to the vulval cells at the L3 lethargus, and subsequent vulval morphogenesis is abnormal. In addition, the
uv1 uterine cells, which play an important role in attaching the uterus to the vulva, are morphologically abnormal. Alleles of
egl-38 exhibit partial tissue-preferential disruption of function.
n578 strongly disrupts egg-laying function (90% of homozytgotes are Egl), but not viability (14% Let). In contrast, 50% of viable
sy294 animals are Egl, but 63% die before reaching adulthood. Based on tests in trans to other alleles,
s1775 disrupts both egg-laying and viability, and may represent a null mutation. We have cloned the
egl-38 locus based on its genetic map position. We mapped
egl-38 to the cluster of LG IV, between
egl-20 and
daf-14. Testing cosmids in the region for transgenic rescue, we identified two that each rescue
egl-38, and overlap by approximately 20 kb of genomic DNA. Using the genomic sequence data for the region provided by the C. elegans sequencing consortium, we identified a candidate gene, C04G2.7. The predicted gene product contains a paired domain, and is most similar to the Pax-2/Pax-5/Pax-8 class of transcription factors. In mammals, genes of this class have also been implicated in mediating fate specification during development. Point mutations in DNA from
egl-38 mutants localize to the Pax gene. Notably, the
n578 mutation results in a substitution of Glu in place of an invariant Gly residue that normally contacts the minor groove of DNA.