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PMID: 20147375 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcriptional control of stem cell maintenance in the Drosophila intestine.

Development (Cambridge, England) ·Vol. 137 ·No. 5 ·2010-03-00 ·Pages 705-14

Bardin AJ, Perdigoto CN, Southall TD, Brand AH, Schweisguth F

Abstract

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.

MeSH Terms
Animals Animals, Genetically Modified Basic Helix-Loop-Helix Transcription Factors/genetics,metabolism,physiology Cell Differentiation/genetics Cell Proliferation Drosophila/genetics,metabolism,physiology Drosophila Proteins/genetics,metabolism,physiology Enteroendocrine Cells/metabolism,physiology Female Gene Expression Regulation, Developmental Intestinal Mucosa/metabolism Intestines/physiology Models, Biological Repressor Proteins/genetics,metabolism,physiology Stem Cells/metabolism,physiology Transcription Factors/genetics,metabolism,physiology Transcription, Genetic/physiology
Chemicals
Basic Helix-Loop-Helix Transcription Factors Da protein, Drosophila Drosophila Proteins E(spl)m7-HLH protein, Drosophila Repressor Proteins Su(H) protein, Drosophila Transcription Factors H protein, Drosophila
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bardin Allison J
Institut Pasteur, CNRS URA2578, 75724 Paris Cedex 15, France. abardin@pasteur.fr
Perdigoto Carolina N
Southall Tony D
Brand Andrea H
Schweisguth François
References (65)
65 references, click to expand
  1. Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors.
    Mol Cell Biol. 2005 Dec;25(23):10433-41 PMID: 16287856
  2. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells.
    Cell. 2008 Jun 27;133(7):1162-74 PMID: 18585351
  3. Transcription factor achaete scute-like 2 controls intestinal stem cell fate.
    Cell. 2009 Mar 6;136(5):903-12 PMID: 19269367
  4. Stonewalling Drosophila stem cell differentiation by epigenetic controls.
    Development. 2007 Apr;134(8):1471-9 PMID: 17344229
  5. Paracrine unpaired signaling through the JAK/STAT pathway controls self-renewal and lineage differentiation of drosophila intestinal stem cells.
    J Mol Cell Biol. 2010 Feb;2(1):37-49 PMID: 19797317
  6. Spatially restricted factors cooperate with notch in the regulation of Enhancer of split genes.
    Dev Biol. 2000 May 15;221(2):390-403 PMID: 10790334
  7. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling.
    Science. 2007 Feb 16;315(5814):988-92 PMID: 17303754
  8. Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development.
    Trends Neurosci. 2001 May;24(5):251-4 PMID: 11311363
  9. Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.
    Genes Dev. 1995 Nov 1;9(21):2609-22 PMID: 7590239
  10. An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3312-7 PMID: 17360644
  11. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine.
    Science. 2001 Dec 7;294(5549):2155-8 PMID: 11739954
  12. A chimeric enhancer-of-split transcriptional activator drives neural development and achaete-scute expression.
    Mol Cell Biol. 1997 Aug;17(8):4355-62 PMID: 9234693
  13. Regulation of notch signaling activity.
    Curr Biol. 2004 Feb 3;14(3):R129-38 PMID: 14986688
  14. Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless.
    Genes Dev. 2002 Aug 1;16(15):1964-76 PMID: 12154126
  15. Gene-specific targeting of the histone chaperone asf1 to mediate silencing.
    Dev Cell. 2007 Oct;13(4):593-600 PMID: 17925233
  16. B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits.
    Mol Cell Biol. 1991 Feb;11(2):1156-60 PMID: 1990271
  17. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells.
    Nature. 2008 Oct 23;455(7216):1119-23 PMID: 18806781
  18. Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila.
    Development. 1996 Jan;122(1):161-71 PMID: 8565827
  19. Role of dpp signalling in prepattern formation of the dorsocentral mechanosensory organ in Drosophila melanogaster.
    Development. 1998 Nov;125(21):4215-24 PMID: 9753676
  20. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling.
    Genes Dev. 1995 Nov 1;9(21):2598-608 PMID: 7590238
  21. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.
    Cell. 2009 Jun 26;137(7):1343-55 PMID: 19563763
  22. wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development.
    Development. 1993 Jun;118(2):427-38 PMID: 8223270
  23. The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.
    Development. 1994 Dec;120(12):3537-48 PMID: 7821220
  24. The choice of cell fate in the epidermis of Drosophila.
    Cell. 1991 Mar 22;64(6):1083-92 PMID: 2004417
  25. Hairless promotes stable commitment to the sensory organ precursor cell fate by negatively regulating the activity of the Notch signaling pathway.
    Dev Biol. 1995 Dec;172(2):479-94 PMID: 8612965
  26. Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless.
    Genes Dev. 1994 Oct 15;8(20):2491-503 PMID: 7958912
  27. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity.
    Genes Dev. 2002 Jun 15;16(12):1488-97 PMID: 12080087
  28. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation.
    Cell Host Microbe. 2009 Feb 19;5(2):200-11 PMID: 19218090
  29. Drosophila stem cells share a common requirement for the histone H2B ubiquitin protease scrawny.
    Science. 2009 Jan 9;323(5911):248-51 PMID: 19039105
  30. The canonical Notch signaling pathway: unfolding the activation mechanism.
    Cell. 2009 Apr 17;137(2):216-33 PMID: 19379690
  31. Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila.
    Curr Biol. 2001 May 15;11(10):789-92 PMID: 11378391
  32. Interactions among the bHLH domains of the proteins encoded by the Enhancer of split and achaete-scute gene complexes of Drosophila.
    Mol Gen Genet. 1996 Jul 26;251(6):628-34 PMID: 8757393
  33. Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin.
    Development. 2006 May;133(9):1683-92 PMID: 16554363
  34. Regulation of expression of Vg and establishment of the dorsoventral compartment boundary in the wing imaginal disc by Suppressor of Hairless.
    Dev Biol. 2006 Jan 1;289(1):77-90 PMID: 16307735
  35. Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless.
    Development. 2005 Aug;132(15):3333-44 PMID: 15975935
  36. Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells.
    Nat Cell Biol. 2008 Jun;10(6):731-9 PMID: 18454139
  37. A network of interacting transcriptional regulators involved in Drosophila neural fate specification revealed by the yeast two-hybrid system.
    Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13099-104 PMID: 9371806
  38. A model Notch response element detects Suppressor of Hairless-dependent molecular switch.
    Curr Biol. 2001 Jan 9;11(1):60-4 PMID: 11166182
  39. Bearded family members inhibit Neuralized-mediated endocytosis and signaling activity of Delta in Drosophila.
    Dev Cell. 2006 Feb;10(2):245-55 PMID: 16459303
  40. Genetic programs activated by proneural proteins in the developing Drosophila PNS.
    Dev Cell. 2005 Mar;8(3):413-25 PMID: 15737936
  41. Mechanisms of asymmetric stem cell division.
    Cell. 2008 Feb 22;132(4):583-97 PMID: 18295577
  42. Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation.
    Development. 2009 Jul;136(13):2255-64 PMID: 19502486
  43. The Hes gene family: repressors and oscillators that orchestrate embryogenesis.
    Development. 2007 Apr;134(7):1243-51 PMID: 17329370
  44. Stem cell regulation by polycomb repressors: postponing commitment.
    Curr Opin Cell Biol. 2008 Apr;20(2):201-7 PMID: 18291635
  45. The adult Drosophila posterior midgut is maintained by pluripotent stem cells.
    Nature. 2006 Jan 26;439(7075):470-4 PMID: 16340960
  46. Context dependence of proneural bHLH proteins.
    Curr Opin Genet Dev. 2008 Oct;18(5):411-7 PMID: 18722526
  47. SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron.
    Nature. 2007 Nov 15;450(7168):415-9 PMID: 17928865
  48. The wingless signalling pathway and the patterning of the wing margin in Drosophila.
    Development. 1994 Mar;120(3):621-36 PMID: 8162860
  49. Double-label in situ hybridization using biotin and digoxigenin-tagged RNA probes.
    Biotechniques. 1994 Nov;17(5):870, 874-5 PMID: 7840966
  50. Evidence that stem cells reside in the adult Drosophila midgut epithelium.
    Nature. 2006 Jan 26;439(7075):475-9 PMID: 16340959
  51. A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology.
    Cell. 2000 Dec 8;103(6):957-69 PMID: 11136980
  52. Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer.
    Genes Dev. 1994 Apr 15;8(8):970-80 PMID: 7926781
  53. Live imaging with green fluorescent protein.
    Methods Mol Biol. 1999;122:241-59 PMID: 10231796
  54. A Notch-independent function of Suppressor of Hairless during the development of the bristle sensory organ precursor cell of Drosophila.
    Development. 2003 May;130(9):1973-88 PMID: 12642500
  55. Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment.
    J Biol Chem. 2005 Jan 14;280(2):1299-305 PMID: 15507447
  56. bHLH proteins encoded by the Enhancer of split complex of Drosophila negatively interfere with transcriptional activation mediated by proneural genes.
    Mol Gen Genet. 1994 Sep 1;244(5):465-73 PMID: 8078474
  57. The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development.
    Genes Dev. 1992 Sep;6(9):1752-69 PMID: 1516831
  58. Repression by suppressor of hairless and activation by Notch are required to define a single row of single-minded expressing cells in the Drosophila embryo.
    Genes Dev. 2000 Feb 1;14(3):377-88 PMID: 10673509
  59. Tissue damage-induced intestinal stem cell division in Drosophila.
    Cell Stem Cell. 2009 Jan 9;4(1):49-61 PMID: 19128792
  60. Dissecting the mechanisms of suppressor of hairless function.
    Dev Biol. 2000 Nov 15;227(2):520-32 PMID: 11071771
  61. Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator.
    Development. 2006 May;133(10):1979-89 PMID: 16624856
  62. Asymmetric localization and function of cell-fate determinants: a fly's view.
    Curr Opin Neurobiol. 2004 Feb;14(1):6-14 PMID: 15018932
  63. Neurogenic and proneural genes control cell fate specification in the Drosophila endoderm.
    Development. 1995 Feb;121(2):393-405 PMID: 7768181
  64. Notch signalling: a simple pathway becomes complex.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89 PMID: 16921404
  65. Proneural gene self-stimulation in neural precursors: an essential mechanism for sense organ development that is regulated by Notch signaling.
    Genes Dev. 1998 Jul 1;12(13):2036-47 PMID: 9649507
Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
1477-9129
DOI
10.1242/dev.039404
Email
abardin@pasteur.fr
Published
2010-03-00
Pages
705-14
Language
English
Region
England
NLM ID
8701744
PMCID
PMC2827683
Subset
IM
Grants
Wellcome Trust · 068055 · United Kingdom
External Links
PubMed source DOI: 10.1242/dev.039404 PMC Full Text View journal details
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