Home LiteratureArticle Details
PMID: 16163386 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal.

The EMBO journal ·Vol. 24 ·No. 19 ·2005-10-05 ·Pages 3504-15

Nyfeler Y, Kirch RD, Mantei N, Leone DP, Radtke F, Suter U, Taylor V

Abstract

Neural stem cells (NSCs) in the postnatal mammalian brain self-renew and are a source of neurons and glia. To date, little is known about the molecular and cellular mechanisms regulating the maintenance and differentiation of these multipotent progenitors. We show that Jagged1 is required by mitotic cells in the subventricular zone (SVZ) and stimulates self-renewal of multipotent epidermal growth factor-dependent NSCs. Jagged1-expressing cells line the adult SVZ and are juxtaposed to Notch1-expressing cells, some of which are putative NSCs. In vitro, endogenous Jagged1 acts through Notch1 to promote NSC maintenance and multipotency. In vivo, reducing Jagged1/Notch1 signaling decreases the number of proliferating cells in the SVZ. In addition, soluble Jagged1 promotes self-renewal and neurogenic potential of multipotent neural progenitors in vitro. Our findings suggest a central role for Jagged1 in the NSC niche in the SVZ for maintaining a population of NSCs in the postnatal brain.

MeSH Terms
Animals Calcium-Binding Proteins/metabolism Cell Differentiation/physiology Cell Proliferation Epidermal Growth Factor/metabolism Fluorescent Antibody Technique Intercellular Signaling Peptides and Proteins Jagged-1 Protein Lateral Ventricles/cytology Membrane Proteins/metabolism Mice Multipotent Stem Cells/cytology,metabolism Receptor, Notch1/metabolism Reverse Transcriptase Polymerase Chain Reaction Serrate-Jagged Proteins Signal Transduction/physiology
Chemicals
Calcium-Binding Proteins Intercellular Signaling Peptides and Proteins Jag1 protein, mouse Jagged-1 Protein Membrane Proteins Notch1 protein, mouse Receptor, Notch1 Serrate-Jagged Proteins Epidermal Growth Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Nyfeler Yves
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Freiburg, Germany.
Kirch Robert D
Mantei Ned
Leone Dino P
Radtke Freddy
Suter Ueli
Taylor Verdon
References (49)
49 references, click to expand
  1. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells.
    Cell. 2000 May 26;101(5):499-510 PMID: 10850492
  2. Isolation of multipotent adult stem cells from the dermis of mammalian skin.
    Nat Cell Biol. 2001 Sep;3(9):778-84 PMID: 11533656
  3. Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2.
    Nat Cell Biol. 2000 Aug;2(8):515-20 PMID: 10934472
  4. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage.
    Development. 2000 Dec;127(24):5253-63 PMID: 11076748
  5. Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods.
    J Biol Chem. 1999 Nov 12;274(46):32961-9 PMID: 10551863
  6. Out of Eden: stem cells and their niches.
    Science. 2000 Feb 25;287(5457):1427-30 PMID: 10688781
  7. Why stem cells?
    Science. 2000 Feb 25;287(5457):1439-41 PMID: 10688784
  8. rax, Hes1, and notch1 promote the formation of Müller glia by postnatal retinal progenitor cells.
    Neuron. 2000 May;26(2):383-94 PMID: 10839357
  9. Radial glial identity is promoted by Notch1 signaling in the murine forebrain.
    Neuron. 2000 May;26(2):395-404 PMID: 10839358
  10. Neurons derived from radial glial cells establish radial units in neocortex.
    Nature. 2001 Feb 8;409(6821):714-20 PMID: 11217860
  11. An instructive function for Notch in promoting gliogenesis in the zebrafish retina.
    Development. 2001 Apr;128(7):1099-107 PMID: 11245575
  12. Neural stem cells.
    Curr Opin Neurobiol. 2001 Oct;11(5):564-7 PMID: 11595489
  13. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations.
    Annu Rev Cell Dev Biol. 2001;17:387-403 PMID: 11687494
  14. Notch1 is required for neuronal and glial differentiation in the cerebellum.
    Development. 2002 Jan;129(2):373-85 PMID: 11807030
  15. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency.
    Development. 2002 Feb;129(4):1075-82 PMID: 11861489
  16. Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells.
    Genes Dev. 2002 Apr 1;16(7):846-58 PMID: 11937492
  17. Astroglia induce neurogenesis from adult neural stem cells.
    Nature. 2002 May 2;417(6884):39-44 PMID: 11986659
  18. Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse.
    Genes Dev. 2002 May 1;16(9):1060-5 PMID: 12000789
  19. Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain.
    Mech Dev. 2002 Jun;114(1-2):153-9 PMID: 12175503
  20. Notch1 control of oligodendrocyte differentiation in the spinal cord.
    J Cell Biol. 2002 Aug 19;158(4):709-18 PMID: 12186854
  21. Little evidence for developmental plasticity of adult hematopoietic stem cells.
    Science. 2002 Sep 27;297(5590):2256-9 PMID: 12215650
  22. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells.
    Neuron. 2002 Dec 19;36(6):1021-34 PMID: 12495619
  23. Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process.
    Development. 2003 Apr;130(7):1391-402 PMID: 12588854
  24. Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells.
    J Neurosci. 2003 Mar 1;23(5):1730-41 PMID: 12629177
  25. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation.
    Cell. 2003 Oct 17;115(2):163-75 PMID: 14567914
  26. The glial identity of neural stem cells.
    Nat Neurosci. 2003 Nov;6(11):1127-34 PMID: 14583753
  27. Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells.
    J Neurosci Res. 2004 Feb 1;75(3):330-43 PMID: 14743446
  28. For the long run: maintaining germinal niches in the adult brain.
    Neuron. 2004 Mar 4;41(5):683-6 PMID: 15003168
  29. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells.
    Science. 2004 May 28;304(5675):1338-40 PMID: 15060285
  30. Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
    Nat Cell Biol. 2004 Jun;6(6):547-54 PMID: 15156153
  31. NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes.
    J Biol Chem. 2004 Jun 11;279(24):25858-65 PMID: 15082708
  32. Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination.
    Brain. 2004 Sep;127(Pt 9):1928-41 PMID: 15289265
  33. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.
    Science. 1992 Mar 27;255(5052):1707-10 PMID: 1553558
  34. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells.
    Neuron. 1994 Nov;13(5):1071-82 PMID: 7946346
  35. Jagged: a mammalian ligand that activates Notch1.
    Cell. 1995 Mar 24;80(6):909-17 PMID: 7697721
  36. Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development.
    Mol Cell Neurosci. 1996;8(1):14-27 PMID: 8923452
  37. Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development.
    Mech Dev. 1996 Oct;59(2):177-90 PMID: 8951795
  38. Conservation of the Notch signalling pathway in mammalian neurogenesis.
    Development. 1997 Mar;124(6):1139-48 PMID: 9102301
  39. Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc.
    Development. 1997 Aug;124(15):2973-81 PMID: 9247339
  40. Notch receptor activation inhibits oligodendrocyte differentiation.
    Neuron. 1998 Jul;21(1):63-75 PMID: 9697852
  41. Stem cells in the developing and adult nervous system.
    J Neurobiol. 1998 Aug;36(2):105-10 PMID: 9712298
  42. Stem cells in the adult mammalian central nervous system.
    Curr Opin Neurobiol. 1999 Feb;9(1):135-41 PMID: 10072370
  43. Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon.
    Dev Biol. 1999 Apr 1;208(1):166-88 PMID: 10075850
  44. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1.
    Hum Mol Genet. 1999 May;8(5):723-30 PMID: 10196361
  45. Deficient T cell fate specification in mice with an induced inactivation of Notch1.
    Immunity. 1999 May;10(5):547-58 PMID: 10367900
  46. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
    Cell. 1999 Jun 11;97(6):703-16 PMID: 10380923
  47. Chipping away at stem cells.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7652-3 PMID: 11438717
  48. The evolving concept of a stem cell: entity or function?
    Cell. 2001 Jun 29;105(7):829-41 PMID: 11439179
  49. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions.
    Nature. 2000 Jul 27;406(6794):411-5 PMID: 10935637
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600816
Published
2005-10-05
Epub
2005-00-15
Pages
3504-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1276174
Subset
IM
Grants
NICHD NIH HHS · N01-HD-7-3263 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7600816 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2