An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons

Hong Liu, Soo-Young Kim, Yulong Fu, Xuefeng Wu, Lily Ng, Anand Swaroop and Douglas Forrest ()
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Hong Liu: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK
Soo-Young Kim: Neurobiology, Neurodegeneration and Repair Laboratory, National Institutes of Health, NEI
Yulong Fu: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK
Xuefeng Wu: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK
Lily Ng: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK
Anand Swaroop: Neurobiology, Neurodegeneration and Repair Laboratory, National Institutes of Health, NEI
Douglas Forrest: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2793

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