RT Journal Article SR Electronic T1 The CB1 Cannabinoid Receptor Drives Corticospinal Motor Neuron Differentiation through the Ctip2/Satb2 Transcriptional Regulation Axis JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 16651 OP 16665 DO 10.1523/JNEUROSCI.0681-12.2012 VO 32 IS 47 A1 Díaz-Alonso, Javier A1 Aguado, Tania A1 Wu, Chia-Shan A1 Palazuelos, Javier A1 Hofmann, Clementine A1 Garcez, Patricia A1 Guillemot, François A1 Lu, Hui-Chen A1 Lutz, Beat A1 Guzmán, Manuel A1 Galve-Roperh, Ismael YR 2012 UL http://www.jneurosci.org/content/32/47/16651.abstract AB The generation and specification of pyramidal neuron subpopulations during development relies on a complex network of transcription factors. The CB1 cannabinoid receptor is the major molecular target of endocannabinoids and marijuana active compounds. This receptor has been shown to influence neural progenitor proliferation and axonal growth, but its involvement in neuronal differentiation and the functional impact in the adulthood caused by altering its signaling during brain development are not known. Here we show that the CB1 receptor, by preventing Satb2 (special AT-rich binding protein 2)-mediated repression, increased Ctip2 (COUP-TF interacting protein 2) promoter activity, and Ctip2-positive neuron generation. Unbalanced neurogenic fate determination found in complete CB1−/− mice and in glutamatergic neuron-specific Nex–CB1−/− mice induced overt alterations in corticospinal motor neuron generation and subcerebral connectivity, thereby resulting in an impairment of skilled motor function in adult mice. Likewise, genetic deletion of CB1 receptors in Thy1–YFP–H mice elicited alterations in corticospinal tract development. Altogether, these data demonstrate that the CB1 receptor contributes to the generation of deep-layer cortical neurons by coupling endocannabinoid signals from the neurogenic niche to the intrinsic proneurogenic Ctip2/Satb2 axis, thus influencing appropriate subcerebral projection neuron specification and corticospinal motor function in the adulthood.