Abstract
Ongoing production of neurons in adult brain is restricted to specialized neurogenic niches. Deregulated expression of genes controlling homeostasis of neural progenitor cell division and/or their microenvironment underpins a spectrum of brain pathologies. Using conditional gene deletion, we show that the proto-oncogene c-myb regulates neural progenitor cell proliferation and maintains ependymal cell integrity in mice. These two cellular compartments constitute the neurogenic niche in the adult brain. Brains devoid of c-Myb showed enlarged ventricular spaces, ependymal cell abnormalities, and reduced neurogenesis. Neural progenitor cells lacking c-Myb showed a reduced intrinsic proliferative capacity and reduction of Sox-2 and Pax-6 expression. These data point to an important role for c-Myb in the neurogenic niche of the adult brain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult Stem Cells / cytology*
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Adult Stem Cells / metabolism
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Animals
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Brain / cytology*
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Brain / embryology
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Brain / metabolism
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Cell Count
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Cell Differentiation / physiology
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Cell Proliferation
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DNA-Binding Proteins / biosynthesis
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Eye Proteins / biosynthesis
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Gene Expression
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Gene Expression Regulation
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Genes, myb*
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Homeodomain Proteins / biosynthesis
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Immunohistochemistry
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In Situ Hybridization
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In Situ Nick-End Labeling
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Mice
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Microscopy, Electron, Scanning
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Neurons / cytology*
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Neurons / metabolism*
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PAX6 Transcription Factor
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Paired Box Transcription Factors / biosynthesis
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RNA, Messenger / analysis
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Repressor Proteins / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction
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SOXB1 Transcription Factors
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Trans-Activators / biosynthesis
Substances
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DNA-Binding Proteins
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Eye Proteins
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Homeodomain Proteins
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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RNA, Messenger
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Repressor Proteins
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Trans-Activators