Peng, G., Yang, S., Zhang, Y., Zhao, Y., Huang, X., Yi, S., Gu, L., Zhu, G., Zheng, K., Zhou, H., Han, K., Zhou, J. (2026). Toll signaling controls stem cell proliferation in intestinal regeneration and tumorigenesis. EMBO Rep. 27(5): 1270--1300.
FlyBase ID
FBrf0264906
Publication Type
Research paper
Abstract
The Drosophila Toll/NF-κB pathway has been extensively studied for its roles in innate immunity and embryonic development. Nevertheless, the regulatory mechanisms underlying Spz/Toll signaling in non-immune contexts remain poorly understood. Here, we demonstrate a critical role for Toll in regulating intestinal stem cell activity through direct transcriptional control of PI3K and Akt in an insulin-independent manner. Time-series transcriptomic analysis of intestinal damage and repair responses reveals that the stress-responsive factor Jumu regulates Spz expression to activate Toll signaling. Disruption of the Jumu/Spz/Toll cascade or PI3K/Akt signaling impairs intestinal regeneration and suppresses tumor growth, and epistasis analysis confirms that PI3K/Akt functions downstream of Toll. Our findings elucidate an autocrine Spz/Toll-mediated mechanism that drives stem cell function via the PI3K/Akt pathway during tissue homeostasis and uncover a critical non-immune role of Toll signaling in both physiological and pathological contexts.
