| First Author | Ghanem N | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 24 | Pages | 8219-30 |
| PubMed ID | 22699903 | Mgi Jnum | J:185576 |
| Mgi Id | MGI:5429444 | Doi | 10.1523/JNEUROSCI.1344-12.2012 |
| Citation | Ghanem N, et al. (2012) The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the Dlx1/Dlx2 Bigene Cluster. J Neurosci 32(24):8219-30 |
| abstractText | 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. |
