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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Role of huntingtin during cortical development

Objectifs

Huntingtin (HTT), the protein mutated in Huntington disease, regulates the transition from neural stem cells to progenitor cells in hippocampal neurogenesis.

Résumé

Hippocampal neurogenesis consists in an addition of new neurons from a resident pool of neural stem cells (NSCs). The newly generated neurons are the cellular substrate to memory, learning and stress regulation. Reduced neurogenesis is accompanied by cognitive decline and emotional disturbances in the elder but also in neurodegeneration conditions such as Huntington disease (HD). Understanding how stem cells maintain quiescence and what direct the transition to progenitor cells will help to design new therapies to sustain neurogenesis and improve cognition and mood balance in the old and diseased brain. In line with our preliminary experiments, we propose that HTT is crucial for the transition from stem to progenitor cells. In the present project we will describe variations of HTT levels along the hippocampal lineage and disclose the role of HTT in the division and quiescence of stem cells. We will also disclose whether these mechanisms are affected in HD mouse model.

Méthodes

cell biology (cell cultures; immunocytochemistry), immunoblotting, histology (immunohistochemistry), imaging.

Références

  • 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, 93, 99-114.
  • Elias S, McGuire JR, Yu H and Humbert S (2015). Huntingtin is required for epithelial polarity through RAB11A mediated apical trafficking of PAR3-aPKC. Plos Biol, 13:e1002142.
  • Ben M’Barek K, Pla P, Orvoen S, Benstaali, Godin JD, Gardier AM, Saudou F, David DJ and Humbert S (2013). Huntingtin Mediates Anxiety/Depression-related Behaviors and Hippocampal Neurogenesis. J Neurosci, 33, 8608-8620.

Contacts

Fabienne Agasse
Email : fabienne.agasse@univ-grenoble-alpes.fr

Mise à jour le 23 mai 2017

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