Article
- The EMBO Journal (2005) 24, 3504 - 3515
- doi:10.1038/sj.emboj.7600816
Published online: 15 September 2005
Subject Categories:
Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal
Yves Nyfeler1, Robert D Kirch1, Ned Mantei2, Dino P Leone2, Freddy Radtke3, Ueli Suter2 and Verdon Taylor1
- Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Freiburg, Germany
- Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
- Ludwig Institute, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
Correspondence to:
Verdon Taylor, Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Stubeweg 51, 79011 Freiburg, Germany. Tel.: +49 761 5108 487; Fax: +49 761 5108 474; E-mail: taylor@immunbio.mpg.de
Received 17 January 2005; Accepted 8 August 2005
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.
Keywords:
- adult neural stem cells,
- jagged signaling,
- neurogenesis
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