cdh-3 encodes a protocadherin required for morphogenesis of the
hyp10 cell. We have extended earlier phenotypic analyses of the
cdh-3(
pk87) loss-of-function mutation, and have found that it confers a weakly penetrant Clr phenotype. Analysis of the 1-2% of
pk87 homozygotes that die with a Clr phenotype reveals that in many of the animals the excretory duct is misshapen and appears refractile, suggesting that defects in the morphogenesis of the duct may be the cause of the Clr phenotype. Indeed, fluid accumulation is first apparent in the region surrounding the duct. A wild-type
cdh-3 gene on an integrated array is able to rescue this phenotype, confirming that it is caused by loss of
cdh-3 function. The low penetrance of the Clr phenotype suggests that under laboratory conditions other gene(s) are able to compensate for the loss of
cdh-3 function, and that these gene(s) share a redundant function with
cdh-3 . To identify such genes we screened for mutations that enhanced the penetrance of the Clr phenotype. We have screened through 1500 F2 animals and identified a mutation,
fe2 , that defines a gene which we have termed
enc-1 ( en hancer of c dh-3 ).
fe2 is a maternal-effect, temperature sensitive mutation. At 20 o C, about fifty percent of the progeny of
enc-1(
fe2)
cdh-3(
pk87) double mutants arrest with a Clr phenotype. At 25 o C, all the progeny arrest with defects in embryonic morphogenesis, with a high proportion displaying enclosure and elongation defects. The presence of a
cdh-3 rescuing transgene effectively reduces the penetrance of the Clr phenotype to zero, demonstrating that
cdh-3 and
enc-1 encode redundant overlapping functions with regard to excretory duct morphogenesis. However, restoring
cdh-3 function has no effect upon the phenotype displayed at 25 o C, indicating that
enc-1 has an additional function that is not compensated by
cdh-3 . We are currently investigating the cellular defects responsible for the embryonic lethality at 25 o C. Preliminary evidence indicates that the hypodermis becomes disorganised during morphogenesis, consistent with the observed enclosure and elongation phenotypes.