Signaling by the Drosophila epidermal growth factor receptor pathway during development

Abstract

The Drosophila epidermal growth factor (EGF) receptor (DER/EGFR) is a single member of the EGFR/ErbB family in the fly genome. The signal peptide and extreme N-terminus is represented in alternative splice forms, encoding two different protein isoforms. The ligands activating the receptor and the signals it transduces represent one of the key channels of communication between cells during development. The general theme emerging from examination of the diverse array of DER functions is that this pathway provides a relatively short-range signaling module among cells. DER signaling that takes place several cells away from the source is the exception. Graded activation of DER expressed by the follicle cells is achieved by the graded distribution of Gurken in the egg. However, in most other cases, activation of DER provides a binary switch, either in the cells adjacent to the ligand source or within the cells producing the processed ligand. The main intracellular signaling pathway activated by DER is the Ras/MAPK pathway. The obligatory use of this pathway for most aspects of DER signaling is implied by the fact that mutations in the intracellular components of the pathway give rise to phenotypes similar to the loss of the receptor or ligand. In most cases of DER signaling, transcriptional activation is the final output, averaging the cumulative levels of DER activation around the circumference of the cell. The actual activation of the DER pathway provides a binary switch, and the output of the switch, in terms of the battery of target genes, depends on the tissue context and on other signaling pathways.