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Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells.
Prasad, Deepti; Illek, Katharina; Fischer, Friedericke; Holstein, Katrin; Classen, Anne-Kathrin.
Afiliação
  • Prasad D; Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany.
  • Illek K; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
  • Fischer F; Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • Holstein K; Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany.
  • Classen AK; Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany.
Elife ; 122023 02 06.
Article em En | MEDLINE | ID: mdl-36744859
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 consistent 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.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Proteínas de Drosophila / Proteínas Quinases JNK Ativadas por Mitógeno / Drosophila melanogaster / Células Epiteliais Tipo de estudo: Prognostic_studies / Screening_studies Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Proteínas de Drosophila / Proteínas Quinases JNK Ativadas por Mitógeno / Drosophila melanogaster / Células Epiteliais Tipo de estudo: Prognostic_studies / Screening_studies Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha