The Role of Sevenless in Drosophila R7 Photoreceptor Specification

The role played by the Sevenless (Sev) Receptor Tyrosine Kinase (RTK) in Drosophila R7 photoreceptor specification has long remained unclear. Another RTK, the Drosophila EGF Receptor (DER) suffices to specify other photoreceptors, so why then is Sev needed for R7? Notch signaling prevents DER from establishing the photoreceptor fate, and our current model is that Sev hyperactivates the DER pathway specifically to overcome this effect of Notch. We find that a Sev/DER chimera that carries the DER intracellular domain functions identically to Sev itself, suggesting that the two RTKs share the same transducing abilities. Sev has a hydrophobic domain ~60 residues from the Methionine, which if it acts as a transmembrane domain would endow N-terminal intracellular sequences through which additional transduction machinery could be engaged. Rather, we find that this domain acts as a signal peptide, and that there is no Sev N-terminal intracellular domain. When DER expression levels are raised, the protein autoactivates, highlighting that Sev remains strictly ligand dependent even though it is expressed at high levels. We provide further evidence of the hyperactivation of the RTK pathway in R7s, and show that activated Sev can substitute for DER function in specification of R3/4 photoreceptors.