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Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2012
Author Osman Dani, Buchon Nicolas, Chakrabarti Sveta, Huang Yu-Ting, Su Wan-Chi, Poidevin Mickaël, Tsai Yu-Chen, Lemaitre Bruno,
Project The Drosophila intestinal epithelium: an immune barrier
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Original article (peer-reviewed)

Journal Journal of cell science
Volume (Issue) 125(Pt 24)
Page(s) 5944 - 9
Title of proceedings Journal of cell science
DOI 10.1242/jcs.113100


The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is involved in the regulation of intestinal stem cell (ISC) activity to ensure a continuous renewal of the adult Drosophila midgut. Three ligands, Unpaired 1, Unpaired 2 and Unpaired 3 (Upd1, Upd2 and Upd3, respectively) are known to activate the JAK/STAT pathway in Drosophila. Using newly generated upd mutants and cell-specific RNAi, we showed that Upd1 is required throughout the fly life to maintain basal turnover of the midgut epithelium by controlling ISC maintenance in an autocrine manner. A role of Upd2 and Upd3 in basal conditions is discernible only in old gut, where they contribute to increased ISC abnormal division. Finally, upon an acute stress such as oral bacterial infection, we showed that Upd3 is released from enterocytes and has an additive effect with Upd2 to promote rapid epithelial regeneration. Taken together, our results show that Upd ligands are required to maintain the midgut homeostasis under both normal and pathological states.