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The Journal of Neuroscience, January 9, 2008, 28(2):434-446; doi:10.1523/JNEUROSCI.4374-07.2008

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Development/Plasticity/Repair
Adult Neurogenesis Requires Smad4-Mediated Bone Morphogenic Protein Signaling in Stem Cells

Dilek Colak,¹ Tetsuji Mori,¹ Monika S. Brill,^1,6 Alexander Pfeifer,² Sven Falk,³ Chuxia Deng,⁴ Rui Monteiro,⁵ Christine Mummery,⁵ Lukas Sommer,³ and Magdalena Götz^1,6

¹Helmhotz Center Munich, German Research Center for Environmental Health, Institute for Stem Cell Research, 85764 Neuherberg/Munich, Germany, ²Institute for Pharmacology and Toxicology, University of Bonn, 53113 Bonn, Germany, ³Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland, ⁴Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, ⁵Developmental Biology, Hubrecht Institute, 3584CT Utrecht, Netherlands, and ⁶Physiological Genomics, University of Munich, 80336 Munich, Germany

Correspondence should be addressed to Dr. Magdalena Götz, Gesellschaft für Strahlung und Umweltforschung, Institute for Stem Cell Research, Ingolstädter Landstrasse 1, 85764 Neuherberg/Munich, Germany. Email: magdalena.goetz{at}gsf.de

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.

Key words: neural stem cells; Olig2; Dlx2; neurogenesis; oligodendrocytes; transplantation

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Received Sept. 24, 2007; revised Nov. 19, 2007; accepted Dec. 1, 2007.

Correspondence should be addressed to Dr. Magdalena Götz, Gesellschaft für Strahlung und Umweltforschung, Institute for Stem Cell Research, Ingolstädter Landstrasse 1, 85764 Neuherberg/Munich, Germany. Email: magdalena.goetz{at}gsf.de

This article has been cited by other articles:

				M. S. Brill, M. Snapyan, H. Wohlfrom, J. Ninkovic, M. Jawerka, G. S. Mastick, R. Ashery-Padan, A. Saghatelyan, B. Berninger, and M. Gotz A Dlx2- and Pax6-Dependent Transcriptional Code for Periglomerular Neuron Specification in the Adult Olfactory Bulb J. Neurosci., June 18, 2008; 28(25): 6439 - 6452. [Abstract] [Full Text] [PDF]

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