The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila

• Published in: Stem cell reports Vol. 14; no. 5; pp. 828 - 844
• Main Authors: Chen, Hsi-Ju, Li, Qi, Nirala, Niraj K., Ip, Y. Tony
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-05-2020; Elsevier
• Subjects: Animals; barrier; Cell Differentiation; Cell Self Renewal; Cytoplasm - metabolism; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enterocytes - cytology; Enterocytes - metabolism; Gap Junctions - metabolism; Homeostasis; intestine; Janus Kinases - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mesh; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; septate junction; signaling; Snakeskin; STAT Transcription Factors - metabolism; stem cells; Trans-Activators - genetics; Trans-Activators - metabolism; Upd3; Yorkie; stem cells; Upd3; intestine; septate junction; signaling; barrier; Snakeskin; Drosophila; Mesh; Yorkie
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2020.03.021

Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other septate junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis.
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•Snakeskin and Mesh are septate junction proteins essential for intestinal homeostasis•Snakeskin and Mesh act in enteroblasts and enterocytes to regulate stem cell division•Snakeskin and Mesh form a complex with and restrict the activity of Yorkie•Loss of Snakeskin and Mesh allows Yorkie to promote Upd3 expression and growth
In this article, Ip and colleagues show that, in adult Drosophila midgut, two smooth septate junction proteins called Snakeskin and Mesh not only provide barrier functions but also regulate intestinal tissue homeostasis, by forming a complex with the Hippo pathway transcription factor Yorkie to negatively regulate the expression of Upd3 that controls tissue growth.