Sevenless: its function and structure in the specification of the Drosophila R7 photoreceptor

Area of Science:

• Developmental Biology
• Molecular Genetics
• Cell Signaling

Background:

• The fly eye comprises hundreds of ommatidia, each with a precise arrangement of photoreceptors and support cells.
• Cell-fate specification in ommatidia development is a classic paradigm in developmental biology.
• The sevenless (sev) mutant, where R7 photoreceptor precursors become support cells, was key to understanding this process.

Purpose of the Study:

• To provide a personal perspective on the historical and molecular studies of the sevenless (sev) pathway.
• To detail the biological role and molecular mechanism of sev in R7 photoreceptor specification.
• To explore the integration of sev signaling with other pathways and its evolutionary context.

Main Methods:

• Molecular genetic studies focusing on the sevenless (sev) mutant phenotype.
• Identification and characterization of the sev receptor tyrosine kinase (RTK) and its ligand Bride of Sevenless (Boss).
• Analysis of signaling integration with Drosophila EGF receptor and Notch pathways.
• Investigation of novel RTK activation mechanisms, including transendocytosis and endosomal pH.

Main Results:

• Sev encodes an RTK, and Boss is its ligand expressed on neighboring R8 photoreceptors.
• Sev signaling integrates with EGFR and Notch pathways to specify R7 photoreceptors, R1/6 photoreceptors, and cone cells.
• A novel RTK activation mechanism involving transendocytosis of Boss and activation in a low-pH endocytic compartment is proposed.
• Evolutionary studies suggest sev and Boss roles are specific to flies (Diptera).

Conclusions:

• The sev/Boss pathway is crucial for cell-fate specification in Drosophila eye development.
• Sev signaling exhibits complex integration with other developmental pathways, leading to diverse cell fates.
• A unique RTK activation mechanism involving endocytosis and pH-dependent conformational changes has been uncovered.
• The evolutionary conservation of R7 photoreceptor specification mechanisms remains an open question.