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Gut healing: haemocytes aid via Sax and Tkv jazzes it down

Nature Cell Biology volume 17, pages 707–709 (2015)Cite this article

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Control of stem cell activity is essential for accurate regeneration. Pathogen- or chemical-induced intestinal damage is now shown to recruit haemocytes expressing bone morphogenetic protein signals that stimulate proliferation of intestinal stem cells and subsequently induce their quiescence, in conjunction with muscle-derived bone morphogenetic proteins. A temporal switch in expression of Type I receptors enables this two-phase response.

The Drosophila intestinal epithelium is a useful model system to investigate the cellular and molecular underpinnings of tissue homeostasis and regeneration3. ISCs interspersed through the intestinal epithelium divide to self-renew and give rise to enteroblasts that differentiate into absorptive enterocytes or enteroendocrine cells. Multiple conserved signalling pathways, including the Jak–Stat and EGFR–MAPK pathways, are activated by tissue damage and stimulate ISC proliferation3. Other studies have pointed to a more complex role for BMP signalling in ISC regulation4,5,6,7. Activation of BMP signalling in Drosophila involves binding of ligands, such as Dpp and Gbb, to the Type I–Type II receptor heterotetramers Tkv–Punt or Sax–Punt, leading to phosphorylation of the transcription factor Mad, which, together with Medea, translocates to the nucleus and regulates gene expression8. Dpp produced from the visceral muscle in the posterior midgut signals through Tkv and Mad to promote quiescence of ISCs during the recovery phase4, whereas Sax induces ISC proliferation6. How BMP signalling orchestrates the two-phase regenerative response remained incompletely understood.

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Figure 1: Temporal control of regeneration by differential Dpp signalling to intestinal stem cells.

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Authors and Affiliations

  1. Lesley N. Weaver and Daniela Drummond-Barbosa are in the Department of Biochemistry and Molecular Biology and the Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA,

    Lesley N. Weaver & Daniela Drummond-Barbosa

  2. Daniela Drummond-Barbosa is also in the Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland, 21205, USA,

    Daniela Drummond-Barbosa

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  1. Lesley N. Weaver
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Correspondence to Daniela Drummond-Barbosa.

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Weaver, L., Drummond-Barbosa, D. Gut healing: haemocytes aid via Sax and Tkv jazzes it down. Nat Cell Biol 17, 707–709 (2015). https://doi.org/10.1038/ncb3178

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