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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Role of huntingtin in stem cells

Objectifs

The objective of the proposed training period is to decipher the role of Huntingtin -the protein mutated in Huntington disease- in different types of progenitor cells.

Résumé

We have previously studied the role of huntingtin (HTT) in cortical progenitors and stem cells of the adult subventricular zone and hippocampus. Our preliminary experiments suggest that down regulation of HTT levels is necessary for the transition from these stem/progenitor cells to newly generated neurons. In the present project, we propose to further describe the variations of HTT levels along these three cell lineages in cell cultures in vitro and by immunohistochemistry and in situ hybridization of mouse brain sections. We will then address 1) how HTT maintains the quiescence in stem cells and 2) determine the molecular mechanisms underlying the variations of HTT levels. To address these questions, we will use primary cultures of progenitor cells that are routinely performed in the laboratory.

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.
  • Lopes C, Aubert S, Bourgois-Rocha F, Barnat M, Rego AC, Déglon N, Perrier AL and Humbert S (2016). Dominant-negative effects of adult-onset huntingtin mutations alter the division of human embryonic stem cells-derived neural cells. PLoS ONE 11(2): e0148680. doi:10.1371/journal.pone.0148680.
  • 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.

Domaines d'expertise requis

Molecular and cellular neurobiology, neural progenitors, stem cells, brain diseases.

Contacts

Fabienne Agasse, MCU UGA
Email : fabienne.agasse@univ-grenoble-alpes.fr
Tél: 04 56 52 05 63

Mise à jour le 6 juin 2019

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