Overactive EGF signaling suppresses a C. elegans pnc-1 egg-laying phenotype independent of known signaling mediators.

Nicotinamide recycling is critical to the development and function of Caenorhabditis elegans. Excess nicotinamide in a pnc-1 nicotinamidase mutant causes the necrosis of uv1 and OLQ cells and a highly penetrant egg laying defect. An EGF receptor (let-23) gain-of-function mutation suppresses the Egl phenotype in pnc-1 animals. However, gain-of-function mutations in either of the known downstream mediators, let-60/ Ras or itr-1, are not sufficient. Phosphatidylcholine synthesis is neither required nor sufficient, in contrast to its role in the let-23gf rescue of uv1 necrosis. The mechanism behind the let-23gf suppression of the pnc-1 Egl phenotype is unknown.