TY  - JOUR
AU  - Udayakumar, Aiswarya
AU  - Stavropoulos, Filippos
AU  - Hadjipanteli, Theodosia
AU  - Peng, Guofan
AU  - Bahuguna, Shivohum
AU  - MacClay, Caitlin
AU  - Lee, Jeffrey Y
AU  - Xiao, Qi
AU  - Xia, Yuxian
AU  - Boutros, Michael
AU  - Zhou, Jun
AU  - Apidianakis, Yiorgos
AU  - Pitsouli, Chrysoula
AU  - Ligoxygakis, Petros
TI  - Toll signalling controls intestinal regeneration in Drosophila.
JO  - Development
VL  - 153
IS  - 2
SN  - 0022-0752
CY  - Cambridge
PB  - The Company of Biologists
M1  - DKFZ-2026-00153
SP  - dev204794
PY  - 2026
AB  - 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.
KW  - Animals
KW  - Drosophila Proteins: metabolism
KW  - Drosophila Proteins: genetics
KW  - Toll-Like Receptors: metabolism
KW  - Toll-Like Receptors: genetics
KW  - Intestines: physiology
KW  - Intestines: cytology
KW  - Regeneration: physiology
KW  - Signal Transduction
KW  - Mitosis
KW  - Stem Cells: cytology
KW  - Stem Cells: metabolism
KW  - Drosophila melanogaster: physiology
KW  - Cell Differentiation
KW  - Proto-Oncogene Proteins c-akt: metabolism
KW  - NF-kappa B: metabolism
KW  - Drosophila (Other)
KW  - Gut (Other)
KW  - Intestinal stem cells (Other)
KW  - Toll (Other)
KW  - Drosophila Proteins (NLM Chemicals)
KW  - Toll-Like Receptors (NLM Chemicals)
KW  - Tl protein, Drosophila (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-akt (NLM Chemicals)
KW  - NF-kappa B (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41552968
DO  - DOI:10.1242/dev.204794
UR  - https://inrepo02.dkfz.de/record/308513
ER  -