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Accéder au plan complet du siteCortical development and Huntington’s disease
Objectifs
The objectives are to characterize the role of HTT in cortical progenitors during embryonic brain development and to identify the consequences of its mutation in these processes.
Résumé
Huntington's disease (HD) is a neurological disease characterized by neurodegeneration of the striatum and cerebral cortex in adults. HD is caused by the mutation of the huntingtin protein (HTT) leading to new toxic functions of mutant HTT and the loss of its normal functions. The combined study of the role of HTT and the consequences of its mutation is therefore crucial to understand the pathophysiological mechanisms of HD. Given the adult onset, most studies have focused on these mechanisms in adult neurons. However, HTT plays an essential role during development as revealed by recent data showing that the mutation or deletion during development are sufficient to induce some HD phenotypes in the cerebral cortex. Our team found that HTT, during this developmental windows, is crucial to proper division of cortical progenitors and migration and morphogenesis of newborn neurons. We thus propose to further characterize the role of HTT and the consequences of its mutation during cortical development.
Méthodes
Murine lines (crossing, genotyping), in utero electroporation, microscopy and videomicroscopy, primary culture (neurons and neuroprogenitors cells), histology (embryonic and post-natal brain sections), immunohistochemistry and immunocytochemistry, molecular biology techniques.
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.
- Molina-Calavita M, Barnat M, Elias S, Aparicio E, Piel M and Humbert S (2014). Mutant huntingtin affects cortical progenitor cell division and development of the mouse neocortex. J Neurosci, 34, 10034-10040.
Domaines d'expertise requis
Cellular biology, molecular biology, neurobiology and brain development.
Contacts
Téléchargement(s)
- GIN_offre-stage-M2_2020-2021_MBarnat_20200608.pdf (PDF, 314 Ko)
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Contacts
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