Sevenless

Sevenless, abbreviated sev, is a receptor tyrosine kinase gene in the fruit fly Drosophila melanogaster. It plays a crucial role in the development of the compound eye by specifying the R7 photoreceptor cell. The name Sevenless derives from the phenotype of sev loss-of-function mutants, in which the seventh photoreceptor fails to be properly specified, resulting in an ommatidium missing its R7 cell. The signaling occurs within the developing ommatidium as a local cell-cell interaction that guides proper eye patterning.

Signaling occurs when the ligand Bride of Sevenless (Boss) is produced by the neighboring R8 photoreceptor. Boss binds to the Sev receptor on R7, causing receptor dimerization and autophosphorylation. This recruits the adaptor protein Drk (the Drosophila homolog of Grb2) and the guanine nucleotide exchange factor Sos, which activate the small GTPase Ras. Activated Ras triggers a mitogen-activated protein kinase (MAPK) cascade through Raf and MEK, leading to transcriptional changes that specify R7 fate. The pathway integrates with other signals and transcription factors to ensure correct cell differentiation within each ommatidium.

Genetic and developmental significance: The sev–boss signaling axis is a classic example of inductive signaling in metazoan development and has been instrumental in understanding receptor tyrosine kinase signaling, ligand-receptor specificity, and cell fate determination. Loss of Sev or Boss produces a missing R7 phenotype, while misregulation can alter photoreceptor patterns. Beyond Drosophila eye development, Sevenless serves as a model for studying the principles of RTK signaling and lateral interactions in tissue patterning.