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

被引:112
作者
Osman, Dani [1 ]
Buchon, Nicolas [1 ]
Chakrabarti, Sveta [1 ]
Huang, Yu-Ting [2 ]
Su, Wan-Chi [2 ]
Poidevin, Mickael [3 ]
Tsai, Yu-Chen [2 ,4 ]
Lemaitre, Bruno [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Global Hlth Inst, Stn 19, CH-1015 Lausanne, Switzerland
[2] Tunghai Univ, Dept Life Sci, Taichung 407, Taiwan
[3] CNRS, CGM, F-91198 Gif Sur Yvette, France
[4] Tunghai Univ, Life Sci Res Ctr, Taichung 407, Taiwan
基金
欧洲研究理事会;
关键词
Intestinal stem cells; JAK/STAT; Proliferation; Upd; Infection; DROSOPHILA MIDGUT; BACTERIAL-INFECTION; PATHWAY; PROLIFERATION; DIFFERENTIATION; HOMEOSTASIS; PROTEIN; LIGAND; GUT;
D O I
10.1242/jcs.113100
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:5944 / 5949
页数:6
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