Spatially Restricted Regulation of Spätzle/Toll Signaling during Cell Competition.

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Cell competition is a mechanism for eliminating less fit cells during development.
• In Drosophila wing discs, this process involves a signaling module including Spätzle (Spz) and Toll receptors to induce apoptosis.
• The precise activation and localization of this signaling module remain unclear.

Purpose of the Study:

• To investigate the activation mechanism of Spz-mediated cell competition in Drosophila wing discs.
• To identify the key molecules involved in triggering the elimination of weaker cells.
• To understand how Spz signaling is restricted to competing cells.

Main Methods:

• Utilized Myc-induced cell competition models in Drosophila.
• Investigated the requirement for local Spz synthesis in loser cell elimination.
• Identified Spz processing enzyme (SPE) and modular serine protease (ModSP) as critical activators.
• Examined the roles of Toll and Toll-8 receptors in Spz-induced apoptosis.

Main Results:

• Demonstrated that local Spz synthesis within the wing disc is essential for loser cell elimination.
• Identified SPE and ModSP as crucial activators of the Spz signaling pathway.
• "Winner" cells enhance SPE production to eliminate nearby wild-type cells.
• Showed that both Toll and Toll-8 receptors are necessary for Spz to induce apoptosis.

Conclusions:

• Spz-mediated cell competition signaling is locally synthesized and activated within the Drosophila imaginal disc.
• Winner cells actively promote the elimination of less fit cells by upregulating SPE.
• This localized signaling ensures tissue integrity without systemic physiological disruption.