CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy

Cell Rep. 2017 Jan 10;18(2):380-390. doi: 10.1016/j.celrep.2016.12.043.

Abstract

During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders.

Keywords: CDYL; RhoA; epilepsy; neuronal migration; transcription.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Brain / pathology
  • Cell Movement
  • Cell Polarity
  • Chromatin / metabolism
  • Co-Repressor Proteins / metabolism
  • Disease Susceptibility
  • Epilepsy / metabolism*
  • Epilepsy / pathology*
  • Gene Knockdown Techniques
  • Histone Acetyltransferases / deficiency*
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism
  • Hydro-Lyases
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Neurons / metabolism*
  • Neurons / pathology*
  • Pentylenetetrazole
  • Polymerization
  • Signal Transduction
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Chromatin
  • Co-Repressor Proteins
  • Histones
  • Histone Acetyltransferases
  • rhoA GTP-Binding Protein
  • Cdyl protein, mouse
  • Hydro-Lyases
  • Pentylenetetrazole