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Centre de recherche

Friday 8 November 2019 from 12:00 at 13:00

Scientific Conference of Friday Noon

Role of autophagy in neuronal migration under normal and pathological conditions

Speaker

  • Armen Saghateylan, PhD
    • Full Professor, Department Psychiatry and Neuroscience, Université Laval
    • Researcher, CERVO Brain Research Centre
    • Canada Research Chair in postnatal neurogenesis

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and a considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. I will present our recent data using time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice showing that decreases in ATP levels force cells into the stationary phase and induce autophagy. Genetic impairment of autophagy in neuroblasts using either inducible conditional mice or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration.

I will next present the data showing that autophagy is altered in disorders linked to neuronal migration defects. Mutations in genes encoding for cadherin ligand/receptor DCHS1 and FAT4 lead to periventricular heterotopias in humans. We observed an impairment of autophagy in human organoids with mutated FAT4 and DCHS1 genes as well as alterations in the migration of mutated human progenitor cells concomitant to a decrease in the number of lysosomes. Thus autophagy is also required for cell migration of human neuronal progenitors and its dysregulation may contribute to migration-associated neurodevelopmental disorders.

 
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Updated on 11/1/2019
Created on 10/23/2019
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