Identification of genes associated with cortical malformation using a transposon-mediated somatic mutagenesis screen in mice.

ABSTRACT: Mutations in genes involved in the production, migration, or differentiation of cortical neurons often lead to malformations of cortical development (MCDs). However, many genetic mutations involved in MCD pathogenesis remain unidentified. Here we developed a genetic screening paradigm based on transposon-mediated somatic mutagenesis by in utero electroporation and the inability of mutant neuronal precursors to migrate to the cortex and identified 33 candidate MCD genes. Consistent with the screen, several genes have already been implicated in neural development and disorders. Functional disruption of the candidate genes by RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human cortical dysplasia. To verify potential clinical relevance of these candidate genes, we ana

SUBMITTER: Lu IL 

PROVIDER: S-EPMC6021418 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature