Abstract

The gut epithelium serves as a physical barrier that prevents infiltration of food-derived harmful substances and microbial contaminations into the body. However, the role of this barrier function in the behavior of gut epithelial cells themselves remains unclear due to the limitation of experimental systems that manipulate epithelial barrier integrity.
In the Drosophila gut epithelium, smooth septate junctions (sSJs) contribute to the barrier function of the epithelium by restricting free diffusion of solutes through the paracellular route. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh and Tsp2A, and found that compromised expression of any of these proteins caused disruption of sSJs and barrier dysfunction in the Drosophila larval gut. Here, we investigated the roles of sSJs in the Drosophila adult gut, whose homeostasis is maintained by the balance between proliferation and differentiation of intestinal stem cells and regeneration of enterocytes differentiated from the stem cells. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and gut barrier dysfunction in flies. Interestingly, the sSJ-protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of IL-6 like cytokines, which are involved in Jak-Stat pathway activation, reduced the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult gut.

Funding

This work was supported by a Grant-in-Aid for Scientific Research (C) to Yasushi Izumi from the Japan Society for the Promotion of Science and by Bioscience Research Grants to Mikio Furuse from the Takeda Science Foundation.

Journal article

Title: Septate junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila

Authors: Yasushi Izumi, Kyoko Furuse and Mikio Furuse
Journal: Journal of Cell Science
Issue: 132 (18)
Date: 26 September 2019
URL (abstract): https://jcs.biologists.org/content/132/18/jcs232108
DOI: 10.1242/jcs.232108