# Toll signalling controls intestinal regeneration in Drosophila

## TL;DR

The study shows that the Toll signaling pathway in fruit flies controls intestinal stem cell division and tissue regeneration.

## Contribution

The paper identifies Toll as a key regulator of intestinal stem cell mitosis and gut bacterial density in Drosophila.

## Key findings

- Toll pathway activation promotes intestinal stem cell mitosis and blocks their differentiation.
- Toll signaling integrates with JNK and Akt/TOR pathways to regulate gut tissue renewal.
- Toll activation suppresses antimicrobial genes, increasing gut bacterial density.

## Abstract

The intestinal interphase is where epithelial renewal and tissue maintenance are balanced alongside immunological regulation. How these functions integrate with cellular signalling is under investigation. Here, we studied the role of the evolutionarily conserved innate immune Toll/NF-κB pathway in Drosophila intestinal regeneration. We found that the core components of the canonical Toll pathway were necessary for intestinal stem cell (ISC) mitosis in homeostasis and upon infection. Toll activation was sufficient to push ISCs into mitosis and the enteroblast (EB) fate, but blocked EB differentiation resulting in ISC and EB accumulation. This was mediated by JNK and Akt/TOR signalling. When JNKK, JNK, Akt or TOR activity was reduced in gut progenitors, ISC mitosis was suppressed. Toll activation also triggered suppression of antimicrobial lysozyme and amidase genes, which led to increased gut bacterial density. Our results identify Toll as necessary and sufficient for ISC mitosis. Our model is that the Toll pathway acts as a regulator of the intestinal landscape integrating JNK and Akt signals to achieve gut tissue renewal and control of commensal bacteria density.

Summary: Toll, a Drosophila homologue of mammalian Toll-like receptors, controls mitosis of intestinal stem cells both following infection and during homeostatic regenerative conditions.