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PMID: 17178400 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord.

Neuron ·Vol. 52 ·No. 6 ·2006-12-21 ·Pages 953-68

Deneen B, Ho R, Lukaszewicz A, Hochstim CJ, Gronostajski RM, Anderson DJ

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.

MeSH Terms
Animals Animals, Genetically Modified Basic Helix-Loop-Helix Transcription Factors/genetics,metabolism Blotting, Western/methods Bromodeoxyuridine/metabolism Cell Differentiation/genetics Chick Embryo Embryo, Mammalian Excitatory Amino Acid Transporter 1/genetics,metabolism Gene Expression Regulation, Developmental/physiology Glial Fibrillary Acidic Protein/metabolism Green Fluorescent Proteins/genetics,metabolism Immunohistochemistry/methods In Situ Hybridization, Fluorescence/methods Mice Microarray Analysis/methods Models, Biological NFI Transcription Factors/physiology Nerve Tissue Proteins/genetics,metabolism Neuroglia/physiology Oligodendrocyte Transcription Factor 2 Organogenesis/physiology RNA Interference/physiology Receptors, Notch/metabolism Spinal Cord/cytology,embryology,physiology Stem Cells/physiology
Chemicals
Basic Helix-Loop-Helix Transcription Factors Excitatory Amino Acid Transporter 1 Glial Fibrillary Acidic Protein NFI Transcription Factors Nerve Tissue Proteins Nfia protein, mouse Olig2 protein, mouse Oligodendrocyte Transcription Factor 2 Receptors, Notch Slc1a3 protein, mouse Green Fluorescent Proteins Bromodeoxyuridine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Deneen Benjamin
Division of Biology 216-76, California Institute of Technology, 1201 East California Boulevard, Pasadena, California 91125, USA.
Ho Ritchie
Lukaszewicz Agnes
Hochstim Christian J
Gronostajski Richard M
Anderson David J
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
Published
2006-12-21
Pages
953-68
Language
English
Region
United States
NLM ID
8809320
Subset
IM
Grants
NINDS NIH HHS · 1F32NS048666 · United States
NINDS NIH HHS · R01-NS23476 · United States
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