RhoGEF2 overexpression induces cell competition dependent on Ptp10D, Crumbs and the Hippo signaling pathway

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• Cell competition eliminates mutant cells in Drosophila, involving polarity proteins like Scrib.
• Signaling pathways like EGFR-Ras, JNK, and Hippo regulate cell competition and apoptosis.
• RhoGEF2 influences Rho signaling and the actin cytoskeleton, but its role in cell competition was unclear.

Purpose of the Study:

• To investigate if RhoGEF2 overexpression (RhoGEF2OE) mimics Scrib depletion in cell competition.
• To elucidate the molecular mechanisms underlying RhoGEF2OE-induced cell elimination.
• To identify key signaling pathways and polarity proteins involved in this process.

Main Methods:

• Utilized Drosophila melanogaster larval epithelial tissues.
• Generated RhoGEF2 overexpression clones and analyzed their interaction with wild-type cells.
• Manipulated Ptp10D and Crb gene expression to assess their impact on RhoGEF2OE-induced cell elimination.
• Assessed JNK, Hippo, and EGFR-Ras signaling pathways.

Main Results:

• RhoGEF2OE cells were eliminated by cell competition when surrounded by wild-type cells.
• Ptp10D knockdown enhanced RhoGEF2OE clone growth and reduced Hippo signaling.
• Mutations in Crb partially rescued RhoGEF2OE clone elimination, normalizing elevated JNK and Hippo signaling and reduced EGFR-Ras signaling.

Conclusions:

• RhoGEF2OE induces cell elimination via cell competition in Drosophila.
• This elimination is dependent on the interplay between Crb, Ptp10D, and Hippo signaling pathways.
• The findings reveal a novel mechanism linking Rho signaling, cell polarity, and cell competition.