Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Chromatin remodelling complexes in cerebral cortex development and neurodevelopmental disorders.

Publication Type

Journal Article

Date of Publication

July 1, 2021

Journal

Neurochemistry international

Volume/Issue

147

ISSN

1872-9754

The diverse number of neurons in the cerebral cortex are generated during development by neural stem cells lining the ventricle, and they continue maturing postnatally. Dynamic chromatin regulation in these neural stem cells is a fundamental determinant of the emerging property of the functional neural network, and the chromatin remodellers are critical determinants of this process. Chromatin remodellers participate in several steps of this process from proliferation, differentiation, migration leading to complex network formation which forms the basis of higher-order functions of cognition and behaviour. Here we review the role of these ATP-dependent chromatin remodellers in cortical development in health and disease and highlight several key mouse mutants of the subunits of the complexes which have revealed how the remodelling mechanisms control the cortical stem cell chromatin landscape for expression of stage-specific transcripts. Consistent with their role in cortical development, several putative risk variants in the subunits of the remodelling complexes have been identified as the underlying causes of several neurodevelopmental disorders. A basic understanding of the detailed molecular mechanism of their action is key to understating how mutations in the same networks lead to disease pathologies and perhaps pave the way for therapeutic development for these complex multifactorial disorders.

Alternate Journal

Neurochem Int

PubMed ID

33964373

PubMed Central ID

PMC7611358

Authors

Leora D'Souza
Asha S Channakkar
Bhavana Muralidharan

Keywords

Gene Expression Regulation, Developmental
Humans
Epigenesis, Genetic
Chromatin
Cerebral Cortex
Chromatin Assembly and Disassembly
Neurodevelopmental Disorders
Animals