title: Coordination of insulin and Notch pathway activities by microRNA miR-305 mediates adaptive homeostasis in the intestinal stem cells of the Drosophila gut.
abstract: Homeostasis of the intestine is maintained by dynamic regulation of a pool of intestinal stem cells. The balance between stem cell self-renewal and differentiation is regulated by the Notch and insulin signaling pathways. Dependence on the insulin pathway places the stem cell pool under nutritional control, allowing gut homeostasis to adapt to environmental conditions. Here we present evidence that miR-305 is required for adaptive homeostasis of the gut. miR-305 regulates the Notch and insulin pathways in the intestinal stem cells. Notably, miR-305 expression in the stem cells is itself under nutritional control via the insulin pathway. This link places regulation of Notch pathway activity under nutritional control. These findings provide a mechanism through which the insulin pathway controls the balance between stem cell self-renewal and differentiation that is required for adaptive homeostasis in the gut in response to changing environmental conditions.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore;
authors.forename: David
authors.initials: D
authors.lastname: Foronda
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore;
authors.forename: Ruifen
authors.initials: R
authors.lastname: Weng
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore;
authors.forename: Pushpa
authors.initials: P
authors.lastname: Verma
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore;
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore scohen@imcb.a-star.edu.sg.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006706:Homeostasis / Q000235:genetics*; D007328:Insulin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; C000594015:MIRN305 microRNA, Drosophila; D035683:MicroRNAs; C497759:N protein, Drosophila; D051880:Receptors, Notch
keywords: Notch; insulin; microRNA; stem cell