Crosstalk between the EGFR and LIN-12/Notch pathways in C-elegans vulval development

The Caenorhabditis elegans vulva is an important paradigm for cell-cell interactions in animal development. The fates of six vulval precursor cells are patterned through the action of the epidermal growth factor receptor - mitogen-activated protein kinase (EGFR-MAPK) inductive signaling pathway, which specifies the 1degrees fate, and the LIN-12/Notch lateral signaling pathway, which specifies the 2degrees fate. Here, we provide evidence that the inductive signal is spatially graded and initially activates the EGFR-MAPK pathway in the prospective 2degrees cells. Subsequently, this effect is counteracted by the expression of multiple new negative regulators of the EGFR-MAPK pathway, under direct transcriptional control of the LIN-12-mediated lateral signal.