Huntingtin-Mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons Is Critical for Their Postnatal Neuronal Morphology
| Autor: | Julien Le Friec, Monia Barnat, Caroline Benstaali, Sandrine Humbert |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Huntingtin Neuronal migration Neocortex Biology Mice 03 medical and health sciences 0302 clinical medicine Cell Movement mental disorders medicine Animals Cerebral Cortex Neurons Huntingtin Protein Transition (genetics) Cadherin General Neuroscience Embryogenesis Cell Polarity Cortical neurons Cadherins nervous system diseases Cortex (botany) Disease Models Animal Protein Transport Huntington Disease 030104 developmental biology medicine.anatomical_structure Animals Newborn nervous system rab GTP-Binding Proteins Peptides Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuron. 93:99-114 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2016.11.035 |
| Popis: | Summary 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 |
| Databáze: | OpenAIRE |
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