| First Author | Stergiopoulos A | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12230 | PubMed ID | 27447294 |
| Mgi Jnum | J:241169 | Mgi Id | MGI:5897943 |
| Doi | 10.1038/ncomms12230 | Citation | Stergiopoulos A, et al. (2016) Nuclear receptor NR5A2 controls neural stem cell fate decisions during development. Nat Commun 7:12230 |
| abstractText | 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. |
