Transcriptional control of stem cell maintenance in the Drosophila intestine.
Adult stem cells maintain tissue homeostasis by controlling the proper balance of stem cell self-renewal and differentiation. The adult midgut of Drosophila contains multipotent intestinal stem cells (ISCs) that self-renew and produce differentiated progeny. Control of ISC identity and maintenance is poorly understood. Here we find that transcriptional repression of Notch target genes by a Hairless-Suppressor of Hairless complex is required for ISC maintenance, and identify genes of the Enhancer of split complex [E(spl)-C] as the major targets of this repression. In addition, we find that the bHLH transcription factor Daughterless is essential to maintain ISC identity and that bHLH binding sites promote ISC-specific enhancer activity. We propose that Daughterless-dependent bHLH activity is important for the ISC fate and that E(spl)-C factors inhibit this activity to promote differentiation.
Bardin
Allison J
AJ
Institut Pasteur, CNRS URA2578, 75724 Paris Cedex 15, France. abardin@pasteur.fr
Perdigoto
Carolina N
CN
Southall
Tony D
TD
Brand
Andrea H
AH
Schweisguth
François
F
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000502:physiology; D008954:Models, Biological; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C090080:Da protein, Drosophila; C121960:E(spl)m7-HLH protein, Drosophila; C088731:Su(H) protein, Drosophila; C076560:H protein, Drosophila