PT  - JOURNAL ARTICLE
AU  - Noël Ghanem
AU  - Matthew G. Andrusiak
AU  - Devon Svoboda
AU  - Sawsan M. Al Lafi
AU  - Lisa M. Julian
AU  - Kelly A. McClellan
AU  - Yves De Repentigny
AU  - Rashmi Kothary
AU  - Marc Ekker
AU  - Alexandre Blais
AU  - David S. Park
AU  - Ruth S. Slack
TI  - The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the <em>Dlx1/Dlx2</em> Bigene Cluster
AID  - 10.1523/JNEUROSCI.1344-12.2012
DP  - 2012 Jun 13
TA  - The Journal of Neuroscience
PG  - 8219--8230
VI  - 32
IP  - 24
4099  - http://www.jneurosci.org/content/32/24/8219.short
4100  - http://www.jneurosci.org/content/32/24/8219.full
SO  - J. Neurosci.2012 Jun 13; 32
AB  - During brain morphogenesis, the mechanisms through which the cell cycle machinery integrates with differentiation signals remain elusive. Here we show that the Rb/E2F pathway regulates key aspects of differentiation and migration through direct control of the Dlx1 and Dlx2 homeodomain proteins, required for interneuron specification. Rb deficiency results in a dramatic reduction of Dlx1 and Dlx2 gene expression manifested by loss of interneuron subtypes and severe migration defects in the mouse brain. The Rb/E2F pathway modulates Dlx1/Dlx2 regulation through direct interaction with a Dlx forebrain-specific enhancer, I12b, and the Dlx1/Dlx2 proximal promoter regions, through repressor E2F sites both in vitro and in vivo. In the absence of Rb, we demonstrate that repressor E2Fs inhibit Dlx transcription at the Dlx1/Dlx2 promoters and Dlx1/2-I12b enhancer to suppress differentiation. Our findings support a model whereby the cell cycle machinery not only controls cell division but also modulates neuronal differentiation and migration through direct regulation of the Dlx1/Dlx2 bigene cluster during embryonic development.