RT Journal Article SR Electronic T1 NFIA Controls Telencephalic Progenitor Cell Differentiation through Repression of the Notch Effector Hes1 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 Michael Piper A1 Guy Barry A1 John Hawkins A1 Sharon Mason A1 Charlotta Lindwall A1 Erica Little A1 Anindita Sarkar A1 Aaron G. Smith A1 Randal X. Moldrich A1 Glen M. Boyle A1 Shubha Tole A1 Richard M. Gronostajski A1 Timothy L. Bailey A1 Linda J. Richards 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.