MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Over the course of cortical neurogenesis, the transition of progenitors from proliferation to differentiation requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory mechanisms, we analyzed microRNA (miRNA) target networks in progenitors during early and late stages of neurogenesis. We found that cyclin D1 is a network hub whose expression is miRNA-dosage sensitive. Experimental validation revealed a feedback regulation between cyclin D1 and its regulating miRNAs miR-20a, miR-20b, and miR-23a. Cyclin D1 induces expression of miR-20a and miR-20b, whereas it represses miR-23a. Inhibition of any of these miRNAs increases the developmental stage-specific mean and dynamic expression range (variance) of cyclin D1 protein in progenitors, leading to reduced neuronal differentiation. Thus, miRNAs establish robustness and stage-specific adaptability to a critical dosage-sensitive gene network during cortical neurogenesis. Understanding such network regulatory mechanisms for key developmental events can provide insights into individual susceptibilities for genetically complex neuropsychiatric disorders.

Details

Original languageEnglish
Pages (from-to)1779-1788
Number of pages10
JournalCell Reports
Volume7
Issue number6
Publication statusPublished - 26 Jun 2014
Peer-reviewedYes

External IDs

Scopus 84903456944
PubMed 24931612
ORCID /0000-0002-8749-7878/work/142251289

Keywords

Research priority areas of TU Dresden

Keywords

  • Animals, Cell Differentiation/genetics, Gene Regulatory Networks, Humans, Mice, Mice, Transgenic, MicroRNAs/genetics, Neurogenesis/genetics, Stem Cells/cytology