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Updated: Dec 22, 2025
Author Spotlight: Investigating the Mechanisms of Neural Circuit Assembly and Synapse Formation in Drosophila
Published on: July 26, 2024
The NMDA receptor regulates competition of epithelial cells in the Drosophila wing
Agnes R Banreti1,2, Pascal Meier3
1The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK. abanreti@unice.fr.
Abstract:
Cell competition is an emerging principle that eliminates suboptimal or potentially dangerous cells. For 'unfit' cells to be detected, their competitive status needs to be compared to the collective fitness of cells within a tissue. Here we report that the NMDA receptor controls cell competition of epithelial cells and Myc supercompetitors in the Drosophila wing disc. While clonal depletion of the NMDA receptor subunit NR2 results in their rapid elimination via the TNF/Eiger>JNK signalling pathway, local over-expression of NR2 causes NR2 cells to acquire supercompetitor-like behaviour that enables them to overtake the tissue through clonal expansion that causes, but also relies on, the killing of surrounding cells. Consistently, NR2 is utilised by Myc clones to provide them with supercompetitor status. Mechanistically, we find that the JNK>PDK signalling axis in 'loser' cells reprograms their metabolism, driving them to produce and transfer lactate to winners. Preventing lactate transfer from losers to winners abrogates NMDAR-mediated cell competition. Our findings demonstrate a functional repurposing of NMDAR in the surveillance of tissue fitness.
Insights
The NMDA receptor (NR2) regulates cell competition in Drosophila, where
Area of Science:
- Developmental Biology
- Cell Biology
- Neuroscience
Background:
- Cell competition eliminates suboptimal cells by comparing their fitness to surrounding cells.
- The mechanisms by which cells assess and act on competitive status are not fully understood.
Purpose of the Study:
- To investigate the role of the NMDA receptor in cell competition within epithelial tissues.
- To elucidate the signaling pathways and metabolic interactions involved in NMDAR-mediated cell competition.
Main Methods:
- Utilized Drosophila wing disc model for studying epithelial cell competition.
- Manipulated NMDA receptor subunit NR2 expression (depletion and overexpression).
- Investigated signaling pathways including TNF/Eiger and JNK>PDK, and lactate metabolism.
Main Results:
- NMDA receptor subunit NR2 controls epithelial cell competition and Myc supercompetitor behavior.
- NR2 depletion leads to cell elimination via TNF/Eiger>JNK signaling.
- NR2 overexpression confers supercompetitor status, promoting clonal expansion and surrounding cell killing.
- JNK>PDK signaling reprograms loser cells to produce and transfer lactate to winner cells.
- Lactate transfer is essential for NMDAR-mediated cell competition.
Conclusions:
- The NMDA receptor is repurposed in epithelial cells to monitor tissue fitness and mediate cell competition.
- A metabolic crosstalk involving lactate transfer between loser and winner cells is crucial for NMDAR-driven competition.
- This study reveals a novel role for NMDARs beyond neuronal function in tissue homeostasis and cell survival decisions.
