Send to

Choose Destination
J Neurosci. 2011 Oct 12;31(41):14794-9. doi: 10.1523/JNEUROSCI.2774-11.2011.

Spatial and temporal requirements for huntingtin (Htt) in neuronal migration and survival during brain development.

Author information

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center