Polycomb‐mediated gene regulation in human brain development and neurodevelopmental disorders

Research output: Contribution to journalReview articleContributedpeer-review

Abstract

The neocortex is considered the seat of higher cognitive function in humans. It develops from a sheet of neural progenitor cells, most of which eventually give rise to neurons. This process of cell fate determination is controlled by precise temporal and spatial gene expression patterns that in turn are affected by epigenetic mechanisms including Polycomb group (PcG) regulation. PcG proteins assemble in multiprotein complexes and catalyze repressive posttranslational histone modifications. Their association with neurodevelopmental disease and various types of cancer of the central nervous system, as well as observations in mouse models, has implicated these epigenetic modifiers in controlling various stages of cortex development. The precise mechanisms conveying PcG-associated transcriptional repression remain incompletely understood and are an active field of research. PcG activity appears to be highly context-specific, raising the question of species-specific differences in the regulation of neural stem and progenitor regulation. In this review, we will discuss our growing understanding of how PcG regulation affects human cortex development, based on studies in murine model systems, but focusing mostly on findings obtained from examining impaired PcG activity in the context of human neurodevelopmental disorders and cancer. Furthermore, we will highlight relevant experimental approaches for functional investigations of PcG regulation in human cortex development.

Details

Original languageEnglish
Pages (from-to)345-363
Number of pages19
JournalDevelopmental Neurobiology
Volume82
Issue number4
Publication statusPublished - 21 Apr 2022
Peer-reviewedYes

External IDs

unpaywall 10.1002/dneu.22876
Scopus 85128578565
Mendeley 158ad9ff-6c71-36e1-9fc8-614d6de5c852
WOSLite 000784388100001

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Subject groups, research areas, subject areas according to Destatis

Sustainable Development Goals

Keywords

  • Polycomb, epigenome editing, gene regulation, neocortex, neurodevelopmental disorder

Library keywords