Nuclear receptor NR5A2 controls neural stem cell fate decisions during development

Athanasios Stergiopoulos and Panagiotis K. Politis ()
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Athanasios Stergiopoulos: Center for Basic Research, Biomedical Research Foundation of the Academy of Athens
Panagiotis K. Politis: Center for Basic Research, Biomedical Research Foundation of the Academy of Athens

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12230

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