Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans.

ABSTRACT: The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling. The complete ablation of Vps15 results in the accumulation of autophagic substrates, the induction of apoptosis and severe cortic

SUBMITTER: Gstrein T 

PROVIDER: S-EPMC5897053 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature