Journal Article DKFZ-2026-00153

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Toll signalling controls intestinal regeneration in Drosophila.

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2026
The Company of Biologists Cambridge

Development 153(2), dev204794 () [10.1242/dev.204794]
 GO

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.

Keyword(s): Animals (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Drosophila Proteins: genetics (MeSH) ; Toll-Like Receptors: metabolism (MeSH) ; Toll-Like Receptors: genetics (MeSH) ; Intestines: physiology (MeSH) ; Intestines: cytology (MeSH) ; Regeneration: physiology (MeSH) ; Signal Transduction (MeSH) ; Mitosis (MeSH) ; Stem Cells: cytology (MeSH) ; Stem Cells: metabolism (MeSH) ; Drosophila melanogaster: physiology (MeSH) ; Cell Differentiation (MeSH) ; Proto-Oncogene Proteins c-akt: metabolism (MeSH) ; NF-kappa B: metabolism (MeSH) ; Drosophila ; Gut ; Intestinal stem cells ; Toll ; Drosophila Proteins ; Toll-Like Receptors ; Tl protein, Drosophila ; Proto-Oncogene Proteins c-akt ; NF-kappa B

Classification:

Contributing Institute(s):
  1. B110 Signalwege funktionelle Genomik (B110)
Research Program(s):
  1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026
Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record
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 Record created 2026-01-20, last modified 2026-01-20



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