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Inter-cell type interactions that control JNK signaling in the Drosophila intestine

Author

Listed:
  • Peng Zhang

    (University of Utah)

  • Stephen M. Pronovost

    (University of Utah)

  • Marco Marchetti

    (University of Utah)

  • Chenge Zhang

    (University of Utah)

  • Xiaoyu Kang

    (University of Utah)

  • Tahmineh Kandelouei

    (University of Utah)

  • Christopher Li

    (University of Utah
    Harvard University)

  • Bruce A. Edgar

    (University of Utah)

Abstract

JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the Drosophila intestine, the TNF-type ligand, Eiger (Egr), is expressed exclusively by intestinal stem cells (ISCs) and enteroblasts (EBs), where it is induced by stress and during aging. Egr preferentially activates JNK signaling in a paracrine fashion in differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N-glycosylation genes (Alg3, Alg9) restrain this activation, and stress-induced downregulation of Alg3 and Alg9 correlates with JNK activation, suggesting a regulatory switch. JNK activity in ECs induces expression of the intermembrane protease Rhomboid (Rho), driving secretion of EGFR ligands Keren (Krn) and Spitz (Spi), which in turn activate EGFR signaling in progenitor cells (ISCs and EBs) to stimulate their growth and division, as well as to produce more Egr. This study uncovers an N-glycosylation-controlled, paracrine JNK-EGFR-JNK feedforward loop that sustains ISC proliferation during stress-induced gut regeneration.

Suggested Citation

  • Peng Zhang & Stephen M. Pronovost & Marco Marchetti & Chenge Zhang & Xiaoyu Kang & Tahmineh Kandelouei & Christopher Li & Bruce A. Edgar, 2024. "Inter-cell type interactions that control JNK signaling in the Drosophila intestine," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49786-w
    DOI: 10.1038/s41467-024-49786-w
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    References listed on IDEAS

    as
    1. Jackson Liang & Shruthi Balachandra & Sang Ngo & Lucy Erin O’Brien, 2017. "Feedback regulation of steady-state epithelial turnover and organ size," Nature, Nature, vol. 548(7669), pages 588-591, August.
    2. Parthive H. Patel & Clothilde Pénalva & Michael Kardorff & Marianne Roca & Bojana Pavlović & Anja Thiel & Aurelio A. Teleman & Bruce A. Edgar, 2019. "Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. Jinyi Xiang & Jennifer Bandura & Peng Zhang & Yinhua Jin & Hanna Reuter & Bruce A. Edgar, 2017. "EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    4. Hansong Deng & Akos A. Gerencser & Heinrich Jasper, 2015. "Signal integration by Ca2+ regulates intestinal stem-cell activity," Nature, Nature, vol. 528(7581), pages 212-217, December.
    5. Ditte S. Andersen & Julien Colombani & Valentina Palmerini & Krittalak Chakrabandhu & Emilie Boone & Michael Röthlisberger & Janine Toggweiler & Konrad Basler & Marina Mapelli & Anne-Odile Hueber & Pi, 2015. "The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth," Nature, Nature, vol. 522(7557), pages 482-486, June.
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