title: Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division.
abstract: 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.
authors.affiliation: Global Health Institute, Station 19, EPFL, 1015 Lausanne, Switzerland. dani.osman@epfl.ch
authors.forename: Dani
authors.initials: D
authors.lastname: Osman
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buchon
authors.forename: Sveta
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Su
authors.forename: Mickaël
authors.initials: M
authors.lastname: Poidevin
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Tsai
authors.forename: Bruno
authors.initials: B
authors.lastname: Lemaitre
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D048708:Cell Growth Processes / Q000502:physiology; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000382:microbiology; D053612:Janus Kinases / Q000378:metabolism; D019899:Paracrine Communication; D016973:Pectobacterium carotovorum / Q000502:physiology; D050791:STAT Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; D053612:Janus Kinases