The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

Cell Mol Life Sci. 2021 Mar;78(6):2517-2563. doi: 10.1007/s00018-020-03714-5. Epub 2020 Dec 2.


Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorders (ASD), are a large group of disorders in which early insults during brain development result in a wide and heterogeneous spectrum of clinical diagnoses. Mutations in genes coding for chromatin remodelers are overrepresented in NDD cohorts, pointing towards epigenetics as a convergent pathogenic pathway between these disorders. In this review we detail the role of NDD-associated chromatin remodelers during the developmental continuum of progenitor expansion, differentiation, cell-type specification, migration and maturation. We discuss how defects in chromatin remodelling during these early developmental time points compound over time and result in impaired brain circuit establishment. In particular, we focus on their role in the three largest cell populations: glutamatergic neurons, GABAergic neurons, and glia cells. An in-depth understanding of the spatiotemporal role of chromatin remodelers during neurodevelopment can contribute to the identification of molecular targets for treatment strategies.

Keywords: Chromatin accessibility; Epigenetics; Neural progenitor; Neurodevelopment; Radial glia; Transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Epigenesis, Genetic
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Neurodevelopmental Disorders / metabolism
  • Neurodevelopmental Disorders / pathology*
  • Neurons / metabolism
  • Protein Processing, Post-Translational / genetics


  • Chromatin
  • Histones
  • DNA Helicases