Abstract
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.
MeSH terms
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Adult Stem Cells / physiology*
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Amino Acid Transport System X-AG / metabolism
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Bone Morphogenetic Proteins / metabolism*
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Bromodeoxyuridine / metabolism
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Carrier Proteins / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Movement / drug effects
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Cell Proliferation* / drug effects
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Cell Transplantation / methods
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Estrogen Antagonists / pharmacology
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Gene Expression Regulation / drug effects
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Glial Fibrillary Acidic Protein / metabolism
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Homeodomain Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Nerve Tissue Proteins / metabolism
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Oligodendrocyte Transcription Factor 2
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Smad4 Protein / deficiency
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Smad4 Protein / physiology*
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Tamoxifen / pharmacology
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Transcription Factors / metabolism
Substances
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Amino Acid Transport System X-AG
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Basic Helix-Loop-Helix Transcription Factors
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Bone Morphogenetic Proteins
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Carrier Proteins
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Distal-less homeobox proteins
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Estrogen Antagonists
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Glial Fibrillary Acidic Protein
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Homeodomain Proteins
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Nerve Tissue Proteins
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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Smad4 Protein
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Smad4 protein, mouse
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Transcription Factors
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Tamoxifen
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noggin protein
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Bromodeoxyuridine