First Author | Liu H | Year | 2013 |
Journal | Nat Commun | Volume | 4 |
Pages | 1813 | PubMed ID | 23652001 |
Mgi Jnum | J:205743 | Mgi Id | MGI:5546314 |
Doi | 10.1038/ncomms2793 | Citation | Liu H, et al. (2013) An isoform of retinoid-related orphan receptor beta directs differentiation of retinal amacrine and horizontal interneurons. Nat Commun 4:1813 |
abstractText | Amacrine and horizontal interneurons integrate visual information as it is relayed through the retina from the photoreceptors to the ganglion cells. The early steps that generate these interneuron networks remain unclear. Here we show that a distinct retinoid-related orphan nuclear receptor beta1 (RORbeta1) isoform encoded by the retinoid-related orphan nuclear receptor beta gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed RORbeta1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. RORbeta1-deficient mice lose expression of pancreas-specific transcription factor 1a (Ptf1a) but retain forkhead box n4 factor (Foxn4), two early-acting factors necessary for amacrine and horizontal cell generation. RORbeta1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for RORbeta1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic RORbeta1 expression in neonatal retina promotes amacrine cell differentiation. |