title: An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons.
abstract: 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 β1 (RORβ1) isoform encoded by the retinoid-related orphan nuclear receptor β gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed RORβ1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. RORβ1-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. RORβ1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for RORβ1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic RORβ1 expression in neonatal retina promotes amacrine cell differentiation.
authors: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK, 10 Center Drive, Bethesda, Maryland 20892-1772, USA.
authors: Hong
authors: H
authors: Liu
authors: Soo-Young
authors: SY
authors: Kim
authors: Yulong
authors: Y
authors: Fu
authors: Xuefeng
authors: X
authors: Wu
authors: Lily
authors: L
authors: Ng
authors: Anand
authors: A
authors: Swaroop
authors: Douglas
authors: D
authors: Forrest
mesh_terms: D000483:Alleles; D025042:Amacrine Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D017353:Gene Deletion; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2 / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D051248:Retinal Horizontal Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; C062602:transcription factor PTF1
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