Inactivation of Lgi1 in murine neuronal precursor cells leads to dysregulation of axon guidance pathways

Research output: Contribution to journalArticle

Abstract

LGI1 mutations predispose to a rare epilepsy syndrome and when inactivated in mice leads to early onset seizures and premature death. Histopathology of the mature brain soon after birth shows cortical dysplasia in Lgi1 null mice with hypercellularity in the outer cortical layers. Here we show extensive gene expression changes in neuronal precursor cells from Lgi1 null mice compared with wild type mice. The most significantly dysregulated pathway involves canonical axon guidance signaling with multiple networks involved in cell movement, adhesion and invasion related to actin cytoskeleton reorganization. The Lgi1 null NPCs show increased cell motility in vitro compared with normal counterparts. Dysregulation of genes critical to cell movement/migration and critical transcription factors involved in early neuronal development is a prominent feature. These studies provide a critical mechanistic link to the observation of increased cellularity in the outer layers of the developing cortex in Lgi1 null mice.

Original languageEnglish (US)
Pages (from-to)1167-1172
Number of pages6
JournalGenomics
Volume112
Issue number2
DOIs
StatePublished - Mar 2020

Keywords

  • Axon guidance
  • Cell migration
  • Gene expression
  • LGI1

ASJC Scopus subject areas

  • Genetics

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