Drosophila activins adapt gut size to food intake and promote regenerative growth

Christian F. Christensen, Quentin Laurichesse, Rihab Loudhaief, Julien Colombani () and Ditte S. Andersen ()
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Christian F. Christensen: University of Copenhagen
Quentin Laurichesse: University of Copenhagen
Rihab Loudhaief: University of Copenhagen
Julien Colombani: University of Copenhagen
Ditte S. Andersen: University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Rapidly renewable tissues adapt different strategies to cope with environmental insults. While tissue repair is associated with increased intestinal stem cell (ISC) proliferation and accelerated tissue turnover rates, reduced calorie intake triggers a homeostasis-breaking process causing adaptive resizing of the gut. Here we show that activins are key drivers of both adaptive and regenerative growth. Activin-β (Actβ) is produced by stem and progenitor cells in response to intestinal infections and stimulates ISC proliferation and turnover rates to promote tissue repair. Dawdle (Daw), a divergent Drosophila activin, signals through its receptor, Baboon, in progenitor cells to promote their maturation into enterocytes (ECs). Daw is dynamically regulated during starvation-refeeding cycles, where it couples nutrient intake with progenitor maturation and adaptive resizing of the gut. Our results highlight an activin-dependent mechanism coupling nutrient intake with progenitor-to-EC maturation to promote adaptive resizing of the gut and further establish activins as key regulators of adult tissue plasticity.

Date: 2024
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DOI: 10.1038/s41467-023-44553-9

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