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EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration

Author

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  • Jinyi Xiang

    (German Cancer Research Center (DKFZ)
    Center for Molecular Biology of The University of Heidelberg (ZMBH))

  • Jennifer Bandura

    (German Cancer Research Center (DKFZ)
    Center for Molecular Biology of The University of Heidelberg (ZMBH))

  • Peng Zhang

    (German Cancer Research Center (DKFZ)
    Center for Molecular Biology of The University of Heidelberg (ZMBH)
    Huntsman Cancer Institute, University of Utah)

  • Yinhua Jin

    (German Cancer Research Center (DKFZ)
    Center for Molecular Biology of The University of Heidelberg (ZMBH))

  • Hanna Reuter

    (Max Planck Institute for Molecular Biomedicine)

  • Bruce A. Edgar

    (German Cancer Research Center (DKFZ)
    Center for Molecular Biology of The University of Heidelberg (ZMBH)
    Huntsman Cancer Institute, University of Utah)

Abstract

Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15125
    DOI: 10.1038/ncomms15125
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