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Huntingtin-Mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons Is Critical for Their Postnatal Neuronal Morphology.

Authors
  • Barnat, Monia1
  • Le Friec, Julien1
  • Benstaali, Caroline1
  • Humbert, Sandrine2
  • 1 University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France. , (France)
  • 2 University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France. Electronic address: [email protected] , (France)
Type
Published Article
Journal
Neuron
Publication Date
Jan 04, 2017
Volume
93
Issue
1
Pages
99–114
Identifiers
DOI: 10.1016/j.neuron.2016.11.035
PMID: 28017473
Source
Medline
Keywords
License
Unknown

Abstract

In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration, and maturation. 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 alters 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. VIDEO ABSTRACT.

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