| First Author | Yu S | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 50 | Pages | 42195-205 |
| PubMed ID | 23105114 | Mgi Jnum | J:327827 |
| Mgi Id | MGI:6834100 | Doi | 10.1074/jbc.M112.410381 |
| Citation | Yu S, et al. (2012) Retinoic acid induces neurogenesis by activating both retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta). J Biol Chem 287(50):42195-205 |
| abstractText | Retinoic acid (RA) regulates gene transcription by activating the nuclear receptors retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR) beta/delta and their respective cognate lipid-binding proteins CRABP-II and FABP5. RA induces neuronal differentiation, but the contributions of the two transcriptional pathways of the hormone to the process are unknown. Here, we show that the RA-induced commitment of P19 stem cells to neuronal progenitors is mediated by the CRABP-II/RAR path and that the FABP5/PPARbeta/delta path can inhibit the process through induction of the RAR repressors SIRT1 and Ajuba. In contrast with its inhibitory activity in the early steps of neurogenesis, the FABP5/PPARbeta/delta path promotes differentiation of neuronal progenitors to mature neurons, an activity mediated in part by the PPARbeta/delta target gene PDK1. Hence, RA-induced neuronal differentiation is mediated through RAR in the early stages and through PPARbeta/delta in the late stages of the process. The switch in RA signaling is accomplished by a transient up-regulation of RARbeta concomitantly with a transient increase in the CRABP-II/FABP5 ratio at early stages of differentiation. In accordance with these conclusions, hippocampi of FABP5-null mice display excess accumulation of neuronal progenitor cells and a deficit in mature neurons versus wild-type animals. |
