RT Journal Article
SR Electronic
T1 NFIA Controls Telencephalic Progenitor Cell Differentiation through Repression of the Notch Effector <em>Hes1</em>
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9127
OP 9139
DO 10.1523/JNEUROSCI.6167-09.2010
VO 30
IS 27
A1 Piper, Michael
A1 Barry, Guy
A1 Hawkins, John
A1 Mason, Sharon
A1 Lindwall, Charlotta
A1 Little, Erica
A1 Sarkar, Anindita
A1 Smith, Aaron G.
A1 Moldrich, Randal X.
A1 Boyle, Glen M.
A1 Tole, Shubha
A1 Gronostajski, Richard M.
A1 Bailey, Timothy L.
A1 Richards, Linda J.
YR 2010
UL http://www.jneurosci.org/content/30/27/9127.abstract
AB 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.