Drosophila EGF receptor signaling: More than a cell fate specification pathway

Abstract

Receptor tyrosine kinase (RTK) signaling is required for cell fate specification, cell proliferation, cell survival and cell morphological changes. EGF receptor (EGFR) activates the canonical Ras/Raf/MAPK pathway during retinal fate specification. EGFR plays roles in cell survival, proliferation, and cell cycle arrest in addition to cell fate specification. My research is focused on the roles of this EGFR/Ras/Raf/MAPK pathway during Drosophila eye development.;The Drosophila ommatidium is founded by initial specification of the R8 neuron cell. The role of EGFR in R8 photoreceptor specification was less clear. My study of Ras, Raf, and pointed, the downstream effectors of the RTK signaling pathway, shows that Ras and Raf, like EGFR are essential for R1-R7 specification but dispensable for R8 specification. My results show that neither EGFR nor any other RTK is essential for R8 specification. However, the EGFR/Ras/Raf pathway affects R8 cell spacing and R8 cell survival.;EGFR is required for both differentiation and G1 arrest of the precluster R2--R5 cells. However, G1 arrest and differentiation are two simultaneous but separable processes. I found the same EGFR/Ras/Raf/MAPK pathway is required for G1 arrest as well as differentiation. Differentiation of the precluster cells requires a higher level of EGFR signaling while G1 arrest requires less EGFR signaling.;EGFR is also required for cell proliferation and survival of the second mitotic wave cells. I found that EGFR regulates cell proliferation and survival without combinatorial input from other signals. The same Ras/Raf/MAPK/Pnt signal transduction pathway is required throughout mitotic and survival responses, although I identified pnt-independent branches regulating mitosis and survival. These pnt-independent branches perhaps can explain how survival and mitosis can occur independently. These results indicated that cells differentiate in response to higher level of EGFR activity, and lower levels of EGFR activity regulate cell cycle and survival outputs.;In addition, I found that Notch antagonizes EGFR signaling in cell survival in pupal eye, and in cell differentiation in column 0. These results suggest that combinatorial input from other signaling pathways might regulate EGFR signaling in those cases.