RT Journal Article SR Electronic T1 Spatial and Temporal Requirements for huntingtin (Htt) in Neuronal Migration and Survival during Brain Development JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 14794 OP 14799 DO 10.1523/JNEUROSCI.2774-11.2011 VO 31 IS 41 A1 Yiai Tong A1 Thomas J. Ha A1 Li Liu A1 Andrew Nishimoto A1 Anton Reiner A1 Dan Goldowitz YR 2011 UL http://www.jneurosci.org/content/31/41/14794.abstract AB Huntington's disease (HD), caused by an expanded triplet repeat in the huntingtin (Htt) gene, results in extensive neuropathology, but study of the Htt gene in CNS development through gene knockout is problematic as the knockout leads to embryonic lethality in mice. Here, we report that the knockdown of Htt expression in neuroepithelial cells of neocortex results in disturbed cell migration, reduced proliferation, and increased cell death that is relatively specific to early neural development. In the cerebellum, however, Htt knockdown results in cell death but not perturbed migration. The cell death phenotype in cortex can be partially reversed with co-knockdown of Casp9, indicating that mitochondria-mediated cell apoptotic processes are involved in the neuronal death. The timing of knockdown during early development is also an important variable. These results indicate a spatial and temporal requirement for Htt expression in neural development. Although it is uncertain whether the loss of wild-type huntingtin function contributes to pathogenesis in Huntington's disease, these results clearly contraindicate the use of nonspecific knockdown of Htt as a therapeutic measure in HD, particularly in utero.