EGL-38/Pax coordinates development in the Caenhorhabditis elegans egg-laying system through EGF pathway dependent and independent functions

Paired box (Pax) proteins function as regulators of coordinated development in organogenesis by controlling factors such as cell growth and differentiation necessary to organize multiple cell types into a single, cohesive organ. Previous work has suggested that Pax transcription factors may regulate diverse cell types through participation in inductive cell-to-cell signaling, which has not been well explored. Here we show that EGL-38, a Pax2/5/8 ortholog, coordinates differentiation of the C. elegans egg-laying system through separate autonomous and non-autonomous functions synchronized by the EGF pathway. We find that EGL-38 protein is expressed at the correct times to both participate in and respond to the EGF pathway specifying uterine ventral (uv1) cell fate, and that EGL-38 is required for uv1 expression of nlp-2 and nlp-7, which are both markers of and participants in uv1 identity. Additionally, we have separated uv1 cell placement and gene expression as distinct hallmarks of uv1 identity and specification, with different dependencies on EGL-38. The parallels between EGL-38 participation in cell signaling events and previous Pax studies argue that coordination of signaling and response to an inductive pathway may be a common feature of Pax protein function.