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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.

Original publication

DOI

10.1523/JNEUROSCI.4374-07.2008

Type

Journal article

Journal

J Neurosci

Publication Date

09/01/2008

Volume

28

Pages

434 - 446

Keywords

Adult Stem Cells, Amino Acid Transport System X-AG, Animals, Basic Helix-Loop-Helix Transcription Factors, Bone Morphogenetic Proteins, Bromodeoxyuridine, Carrier Proteins, Cell Differentiation, Cell Movement, Cell Proliferation, Cell Transplantation, Estrogen Antagonists, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Homeodomain Proteins, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Signal Transduction, Smad4 Protein, Tamoxifen, Transcription Factors