title: EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells.
abstract: Tissue-specific adult stem cells are commonly associated with local niche for their maintenance and function. In the adult Drosophila midgut, the surrounding visceral muscle maintains intestinal stem cells (ISCs) by stimulating Wingless (Wg) and JAK/STAT pathway activities, whereas cytokine production in mature enterocytes also induces ISC division and epithelial regeneration, especially in response to stress. Here we show that EGFR/Ras/ERK signaling is another important participant in promoting ISC maintenance and division in healthy intestine. The EGFR ligand Vein is specifically expressed in muscle cells and is important for ISC maintenance and proliferation. Two additional EGFR ligands, Spitz and Keren, function redundantly as possible autocrine signals to promote ISC maintenance and proliferation. Notably, over-activated EGFR signaling could partially replace Wg or JAK/STAT signaling for ISC maintenance and division, and vice versa. Moreover, although disrupting any single one of the three signaling pathways shows mild and progressive ISC loss over time, simultaneous disruption of them all leads to rapid and complete ISC elimination. Taken together, our data suggest that Drosophila midgut ISCs are maintained cooperatively by multiple signaling pathway activities and reinforce the notion that visceral muscle is a critical component of the ISC niche.
authors: Department of Pediatrics (Neonatology), Duke University, Durham, NC 27710, USA.
authors: Na
authors: N
authors: Xu
authors: Si Qi
authors: SQ
authors: Wang
authors: Dan
authors: D
authors: Tan
authors: Yawei
authors: Y
authors: Gao
authors: Guonan
authors: G
authors: Lin
authors: Rongwen
authors: R
authors: Xi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007422:Intestines / Q000166:cytology; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C465500:Krn protein, Drosophila; D008565:Membrane Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; C076026:spi protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D053612:Janus Kinases; C085845:hop protein, Drosophila; D018631:ras Proteins