Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells

被引:205
作者
Colak, Dilek [1 ]
Mori, Tetsuji [1 ]
Brill, Monika S. [1 ,6 ]
Pfeifer, Alexander [2 ]
Falk, Sven [3 ]
Deng, Chuxia [4 ]
Monteiro, Rui [5 ]
Mummery, Christine [5 ]
Sommer, Lukas [3 ]
Goetz, Magdalena [1 ,6 ]
机构
[1] Inst Stem Cell Res, Gesell Strahlung & Unweltforsch, Helmhotz Ctr Munich, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
[2] Univ Bonn, Inst Pharmacol & Toxicol, D-53113 Bonn, Germany
[3] Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland
[4] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA
[5] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[6] Univ Munich, D-80336 Munich, Germany
关键词
neural stem cells; Olig2; Dlx2; neurogenesis; oligodendrocytes; transplantation;
D O I
10.1523/JNEUROSCI.4374-07.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.
引用
收藏
页码:434 / 445
页数:12
相关论文
共 67 条
[1]   A unified hypothesis on the lineage of neural stem cells [J].
Alvarez-Buylla, A ;
García-Verdugo, JM ;
Tramontin, AD .
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (04) :287-293
[2]   Signal transduction by the TGF-β superfamily [J].
Attisano, L ;
Wrana, JL .
SCIENCE, 2002, 296 (5573) :1646-1647
[3]   Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons [J].
Balordi, Francesca ;
Fishell, Gord .
JOURNAL OF NEUROSCIENCE, 2007, 27 (22) :5936-5947
[4]   Leukemia inhibitory factor promotes neural stem cell self-renewal in the adult brain [J].
Bauer, Sylvian ;
Patterson, Paul H. .
JOURNAL OF NEUROSCIENCE, 2006, 26 (46) :12089-12099
[5]   Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells [J].
Berninger, Benedikt ;
Guillemot, Francois ;
Goetz, Magdalena .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2007, 25 (09) :2581-2590
[6]   Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton [J].
Brunet, LJ ;
McMahon, JA ;
McMahon, AP ;
Harland, RM .
SCIENCE, 1998, 280 (5368) :1455-1457
[7]   Expression pattern of the transcription factor Olig2 in response to brain injuries:: Implications for neuronal repair [J].
Buffo, A ;
Vosko, MR ;
Ertürk, D ;
Hamann, GF ;
Jucker, M ;
Rowitch, D ;
Götz, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (50) :18183-18188
[8]   Isolation of a novel platelet-derived growth factor-responsive precursor from the embryonic ventral forebrain [J].
Chojnacki, A ;
Weiss, S .
JOURNAL OF NEUROSCIENCE, 2004, 24 (48) :10888-10899
[9]   Retroviral manipulation of the expression of bone morphogenetic protein receptor Ia by SVZa progenitor cells leads to changes in their p19INK4d expression but not in their neuronal commitment [J].
Coskun, V ;
Venkatraman, G ;
Yang, H ;
Rao, MS ;
Luskin, MB .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2001, 19 (02) :219-227
[10]   NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS [J].
Dawson, MRL ;
Polito, A ;
Levine, JM ;
Reynolds, R .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2003, 24 (02) :476-488