NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1

Piper, Michael, Barry, Guy, Hawkins, John, Mason, Sharon, Lindwall, Charlotta, Little, Erica, Sarkar, Anindita, Smith, Aaron G., Moldrich, Randal X., Boyle, Glen M., Tole, Shubjha, Gronostajski, Richard M., Bailey, Timothy L. and Richards, Linda J. (2010) NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1. Journal of Neuroscience, 30 27: 9127-9139. doi:10.1523/JNEUROSCI.6167-09.2010

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Author Piper, Michael
Barry, Guy
Hawkins, John
Mason, Sharon
Lindwall, Charlotta
Little, Erica
Sarkar, Anindita
Smith, Aaron G.
Moldrich, Randal X.
Boyle, Glen M.
Tole, Shubjha
Gronostajski, Richard M.
Bailey, Timothy L.
Richards, Linda J.
Title NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1
Formatted title
NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2010-07-01
Year available 2010
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.6167-09.2010
Open Access Status File (Publisher version)
Volume 30
Issue 27
Start page 9127
End page 9139
Total pages 13
Editor John H. R. Maunsell
Place of publication New York, U.S.A.
Publisher Society for Neuroscience
Language eng
Abstract The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these fundamental processes are mechanistically linked, and specifically how repression of progenitor self-renewal pathways occurs, is poorly understood. Nuclear factor I A (Nfia), a gene known to regulate spinal cord and neocortical development, has recently been implicated as acting downstream of Notch to initiate the expression of astrocyte-specific genes within the cortex. Here we demonstrate that, in addition to activating the expression of astrocyte-specific genes, Nfia also downregulates the activity of the Notch signaling pathway via repression of the key Notch effector Hes1. These data provide a significant conceptual advance in our understanding of neural progenitor differentiation, revealing that a single transcription factor can control both the activation of differentiation genes and the repression of the self-renewal genes, thereby acting as a pivotal regulator of the balance between progenitor and differentiated cell states.
Formatted abstract
The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these fundamental processes are mechanistically linked, and specifically how repression of progenitor self-renewal pathways occurs, is poorly understood. Nuclear factor I A (Nfia), a gene known to regulate spinal cord and neocortical development, has recently been implicated as acting downstream of Notch to initiate the expression of astrocyte-specific genes within the cortex. Here we demonstrate that, in addition to activating the expression of astrocyte-specific genes, Nfia also downregulates the activity of the Notch signaling pathway via repression of the key Notch effector Hes1. These data provide a significant conceptual advance in our understanding of neural progenitor differentiation, revealing that a single transcription factor can control both the activation of differentiation genes and the repression of the self-renewal genes, thereby acting as a pivotal regulator of the balance between progenitor and differentiated cell states.
Copyright © 2010 the authors.
Keyword Nuclear factor-i
Fibrillary acidic protein
Astrocyte-specific expression
Central-nervous-system
Gene-expressopm
Radial glia
Negative autoregulation
Postmitotic neurons
Neural progenitors
Promotor elements
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 63 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 25 Jul 2010, 10:05:10 EST