Content

x

Search in this site

Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

  • Linkedin
  • Twitter
  • Youtube

Home > About us > News > Team Humbert News

See the complete sitemap

Huntingtin, an essential protein for the assembly of the cerebral cortex

on the January 23, 2017

Huntingtin-mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons is Critical for their Postnatal Neuronal Morphology

In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration and differentiation. The contribution of these developmental steps to the structure of the adult cortex is not completely understood. Here, we report that huntingtin (HTT), the protein mutated in Huntington’s disease, is enriched in polarizing projection neurons. The depletion of HTT in postmitotic projection neurons leads to the mislocalization of layer-specific neuronal populations in the mouse neocortex. HTT is required for the multipolar-bipolar transition of projection neurons and for the maintenance of their bipolar shape during their radial migration. 

HTT mediates these effects in vivo through the regulation of RAB11-dependent N-Cadherin trafficking. Importantly, HD pathological HTT altered RAB11-dependent neuronal migration. Finally, we show that the cortical defects resulting from the postmitotic loss of HTT specifically during embryonic development affect neuronal morphology at adulthood. Our data reveal a new HTT-RAB11-N-Cadherin pathway regulating multipolar-bipolar transition with direct implications for mature brain.

 


Reference :
Barnat M, Le Friec J, Benstaali C and Humbert S, (2017). Huntingtin-mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons is Critical for their Postnatal Neuronal Morphology. Neuron, Volume 93, Issue 1, p99–114.


Updated on December 8, 2017

Membres
Associés renforcés
Associés simples