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Nat Commun. 2016 Jul 22;7:12230. doi: 10.1038/ncomms12230.

Nuclear receptor NR5A2 controls neural stem cell fate decisions during development.

Author information

1
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Street, 115 27 Athens, Greece.

Abstract

The enormous complexity of mammalian central nervous system (CNS) is generated by highly synchronized actions of diverse factors and signalling molecules in neural stem/progenitor cells (NSCs). However, the molecular mechanisms that integrate extrinsic and intrinsic signals to control proliferation versus differentiation decisions of NSCs are not well-understood. Here we identify nuclear receptor NR5A2 as a central node in these regulatory networks and key player in neural development. Overexpression and loss-of-function experiments in primary NSCs and mouse embryos suggest that NR5A2 synchronizes cell-cycle exit with induction of neurogenesis and inhibition of astrogliogenesis by direct regulatory effects on Ink4/Arf locus, Prox1, a downstream target of proneural genes, as well as Notch1 and JAK/STAT signalling pathways. Upstream of NR5a2, proneural genes, as well as Notch1 and JAK/STAT pathways control NR5a2 endogenous expression. Collectively, these observations render NR5A2 a critical regulator of neural development and target gene for NSC-based treatments of CNS-related diseases.

PMID:
27447294
PMCID:
PMC4961839
DOI:
10.1038/ncomms12230
[Indexed for MEDLINE]
Free PMC Article

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