EGF signaling overcomes a uterine cell death associated with temporal mis-coordination of organogenesis within the C. elegans egg-laying apparatus.

We isolated cog-3(ku212) as a C. elegans egg-laying defective mutant that is associated with a connection-of-gonad defective phenotype. cog-3(ku212) mutants appear to have no connection between the vulval and the uterine lumens at the appropriate stage because the uterine lumen develops with a temporal delay relative to the vulva and, thus, is not present when the connection normally forms. The lack of temporal synchronization between the vulva and the uterus is not due to precocious or accelerated vulval development. Instead, global gonadogenesis is mildly delayed relative to development of extra-gonadal tissue. cog-3(ku212) mutants also have a specific uterine fate defect. Normally, four cells of the uterine pi lineage respond via their LET-23 epidermal growth factor-like receptors to a vulval-derived LIN-3 EGF signal and adopt the uterine vulval 1 (uv1) fate. In cog-3(ku212) mutants, these four pi progeny cells are set aside as a pre-uv1 population but undergo necrosis prior to full differentiation. A gain-of-function mutation in LET-23 EGF receptor and ectopic expression of LIN-3 EGF within the proper temporal constraints can rescue the uv1 defect, suggesting that a signaling defect, perhaps due to the temporal delay, is at fault. In support of this model, we demonstrate that lack of vulval-uterine coordination due to precocious vulval development also leads to uv1 cell differentiation defects.