Abstract
The mechanisms controlling the transition from neurogenesis to gliogenesis in the vertebrate CNS are incompletely understood. We identified a family of transcription factors, called NFI genes, which are induced throughout the spinal cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of neurogenesis in VZ progenitors. This function is mediated by the requirement of NFIA for the expression of HES5, a Notch effector. However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA links the abrogation of neurogenesis to a generic program of gliogenesis, in both astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Blotting, Western / methods
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Bromodeoxyuridine / metabolism
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Cell Differentiation / genetics
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Chick Embryo
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Embryo, Mammalian
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Excitatory Amino Acid Transporter 1 / genetics
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Excitatory Amino Acid Transporter 1 / metabolism
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Gene Expression Regulation, Developmental / physiology*
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Immunohistochemistry / methods
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In Situ Hybridization, Fluorescence / methods
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Mice
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Microarray Analysis / methods
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Models, Biological
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NFI Transcription Factors / physiology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuroglia / physiology*
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Oligodendrocyte Transcription Factor 2
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Organogenesis / physiology*
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RNA Interference / physiology
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Receptors, Notch / metabolism
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Spinal Cord* / cytology
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Spinal Cord* / embryology
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Spinal Cord* / physiology
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Stem Cells / physiology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Excitatory Amino Acid Transporter 1
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Glial Fibrillary Acidic Protein
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NFI Transcription Factors
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Nerve Tissue Proteins
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Nfia protein, mouse
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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Receptors, Notch
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Slc1a3 protein, mouse
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Green Fluorescent Proteins
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Bromodeoxyuridine