Fig. 2. Different modes of EGFR signaling. Although the same canonical EGFR signaling pathway is used in numerous developmental settings, subtle alterations in its regulatory circuitry lead to distinct modes of signaling. (A) A single signaling burst. In this mode, ligand processing is confined to the cells expressing rhomboid (RHO, orange). Secreted ligand is presented to neighboring cells, and the induction of negative-feedback loops (red) confines the signaling zone (green). This is the simplest, and most commonly used, EGFR signaling mode. The figure depicts EGFR signaling in the Drosophila embryonic ventral ectoderm, where rho is expressed in the midline glial cells. (B) Multiple activation cycles from a fixed source. Induction of Argos expression in the cells immediately adjacent to the cleaved ligand source limits the range of activation. Once these cells delaminate, the signal from the original source can now reach the next ring of cells, giving rise to a cyclic pattern of EGFR activation. This mode was first described in the induction of embryonic oenocyte cell fates. (C) Multiple activation cycles from an expanding source. This mode operates during the development of the Drosophila eye, and relies on the expansion of rho expression. A different cell type is induced following each round of EGFR activation, by combining EGFR signaling with distinct transcriptional cues that are unique to each cell type. Each burst of EGFR activation has to be discrete in space and time. (D) The relay of signal source. When signaling takes place between two cell types, rho induction in the cells where EGFR is activated converts them to a signaling source. This response leads to amplification of the original signal, and extends signaling over time, even after the original signal source can no longer be detected. This type of signaling occurs during Drosophila oogenesis, and in C. elegans during vulval cell fate induction. The figure shows a Drosophila egg chamber, where Gurken signal emanating from the oocyte leads to EGFR activation in the follicle cells. The convergence of EGFR and BMP (DPP) signaling from the stretch follicle cells induces rho expression in the dorsal anterior follicle cells, which generates cleaved Spitz in these cells to amplify the signal. Anteroposterior (AP) and dorsoventral (DV) axes are indicated.