Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells

Abstract

Tissue-intrinsic defense mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. 'Interface surveillance' comprises one such distinct mechanism that specifically guards against aberrant cells which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown. We find that in Drosophila imaginal discs, clones of cells with inappropriate activation of cell fate programs induce bilateral JNK activation at clonal interfaces, where wild type and aberrant cells make contact. JNK-activation is required to drive apoptotic elimination of interface cells. Importantly, JNK-activity and apoptosis are highest in interface cells within small aberrant clones, which likely supports the successful elimination of aberrant cells when they arise. Our findings are consitent with a model where clone size affects the topology of interface contacts and thereby the strength of JNK activation in wild type and aberrant interface cells. Bilateral JNK activation is unique to 'interface surveillance' and is not observed in other tissue-intrinsic defense mechanisms, such as classical 'cell-cell competition'. Thus, bilateral JNK interface signaling provides an independent tissue-level mechanism to eliminate cells with inappropriate developmental fate but normal cellular fitness. Finally, oncogenic Ras-expressing clones activate 'interface surveillance' but evade elimination by bilateral JNK activation. Combined, our work establishes bilateral JNK interface signaling and interface apoptosis as a new hallmark of interface surveillance, and highlights how oncogenic mutations evade tumor suppressor function encoded by this tissue-intrinsic surveillance system.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1, 2, 4, 5, 6 and S1, S2.1, S2.2, S5 and S6.1 .

Article and author information

Author details

  1. Deepti Prasad

    Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Katharina Illek

    Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Friedericke Fischer

    Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Katrin Holstein

    Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1540-8378
  5. Anne-Kathrin Classen

    Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany
    For correspondence
    anne.classen@biologie.uni-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5157-0749

Funding

Deutsche Forschungsgemeinschaft (CRC850/A08)

  • Anne-Kathrin Classen

Deutsche Forschungsgemeinschaft (CL490/3-1)

  • Anne-Kathrin Classen

Deutsche Forschungsgemeinschaft (CIBSS-390939984)

  • Anne-Kathrin Classen

Deutsche Forschungsgemeinschaft (SGBM-GSC-4)

  • Deepti Prasad

Boehringer Ingelheim Fonds (BIF Plus3)

  • Anne-Kathrin Classen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Prasad et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Deepti Prasad
  2. Katharina Illek
  3. Friedericke Fischer
  4. Katrin Holstein
  5. Anne-Kathrin Classen
(2023)
Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
eLife 12:e80809.
https://doi.org/10.7554/eLife.80809

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https://doi.org/10.7554/eLife.80809