Fig. 3. Diverse interactions between EGFR and Notch signaling. (A) During the development of distinct cell types in the Drosophila eye, combined inputs from the EGFR pathway (through Pointed) and the Notch (N) pathway [through SU(H)], in conjunction with distinct transcription factors, induce the relevant target genes. For example, the two pathways in conjunction with Lozenge (LZ), induce Drosophila Pax2 (shaven - FlyBase) expression in the future cone cells. (B) The combined activities of EGFR and Notch signaling integrated in a `feed-forward' loop. EGFR activation in the Drosophila photoreceptor (R) cells induces Delta (DL) expression. The combination of the Spitz and DL ligands presented by the R cells induces the cone cell fate, by triggering target gene expression, such as that of Drosophila Pax2. N pathway activation is marked by an open arrow. (C) Mutual repression between the EGFR and Notch pathways refines cell fates during C. elegans vulval development. The anchor cell provides the EGFR ligand (LIN-3) to the primary vulval precursor cell (VPC, green). EGFR signaling in this cell leads to DSL expression (a Notch ligand) and reduces the capacity of the cell to respond to N activation. This cell displays DSL to the secondary VPCs. N signaling in these cells triggers repressors of EGFR signaling (red), thus eliminating their responses to lower levels of the EGFR ligand presented by the anchor cell. In parallel, EGFR activation represses the expression of the receptor tyrosine phosphatase DEP-1 in the primary VPC, whereas a Notch-independent mechanism induces DEP-1 expression in the secondary VPCs. (D) A similar circuit of mutual repression during the determination of vein versus inter-vein fates in the Drosophila wing. Restricted expression of rhomboid only in the future vein cells leads to localized, autocrine EGFR activation (green) and induction of DL expression. EGFR signaling also reinforces the expression of rhomboid. In parallel, MAPK activation by EGFR in these cells can phosphorylate and attenuate the activity of Groucho, which is involved in executing the transcriptional repression responses elicited by N signaling. EGFR activation also eliminates the HMG-box transcriptional repressor Capicua (CIC). In the adjacent inter-vein cells, rhomboid expression is repressed by N signaling, and CIC represses other vein-specific genes. Thus, EGFR signaling is confined to the veins, whereas N signaling is restricted to the intervein cells.