Distinct requirements for the C. elegans Delta ligand APX-1 in embryonic viability and adult fertility

Requirements for the Caenorhabditis elegans Notch ligand APX-1 have been described, but the molecular lesions in mutant alleles remain unknown. Here we report the sequence changes in 3 previously isolated nonconditional alleles and 2 newly isolated alleles, apx-1(or545ts) and a null allele apx-1(or2015). All alleles resulted in highly penetrant embryonic lethality, but only null mutations greatly reduced brood sizes. This reproductive phenotype was likely due to abnormal ovulation rupturing oocytes and, together with vulva defects, resulting in debris accumulation that prevented embryo passage. In addition to identifying molecular lesions in apx-1 alleles and clarifying distinct requirements for C. elegans Notch ligands, our results reveal extensive genotype-by-environment interactions, including haplo-insufficiency of essential loci at a stressfully high growth temperature, and highlight the origins of complex phenotypes as a consequence of multiple seemingly unrelated defects.