Dataset Information

An isoform of retinoid-related orphan receptor ? 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 ?1 (ROR?1) isoform encoded by the retinoid-related orphan nuclear receptor ? gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed ROR?1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. ROR?1-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. ROR?1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for ROR?1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic ROR?1 expression in neonatal retina promotes amacrine cell differentiation.

SUBMITTER: Liu H

PROVIDER: S-EPMC3671912 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Hong H Kim Soo-Young SY Fu Yulong Y Wu Xuefeng X Ng Lily L Swaroop Anand A Forrest Douglas D

Nature communications 20130101

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 ...[more]

PMID: 23652001

Similar Datasets

Project description:The vertebrate retina uses diverse neuronal cell types arrayed into complex neural circuits to extract, process and relay information from the visual scene to the higher order processing centers of the brain. Amacrine cells, a diverse class of inhibitory interneurons, are thought to mediate the majority of the processing of the visual signal that occurs within the retina. Despite morphological characterization, the number of known molecular markers of amacrine cell types is still much smaller than the 26 morphological types that have been identified. Furthermore, it is not known how this diversity arises during development. Here, we have combined in vivo genetic labeling and single cell genome-wide expression profiling to: 1) Identify specific molecular types of amacrine cells; 2) Demonstrate the molecular diversity of the amacrine cell class. It is difficult to identify new markers of amacrine cells, due to the fact that they only comprise a small percentage of the total cells in the retina. Additionally, given that there are at least 26 distinct types of amacrine cells, population based approaches fail to achieve the precision necessary to discover markers of each type. To facilitate the identification of new markers for different amacrine cell classes and to more fully characterize the molecular signatures of these classes, we isolated single amacrine cells. To accomplish this goal, we introduced genetic reporters (pNdrg4::GFP or pSynapsin::GFP) into the developing retina (P0) by either in vivo or ex vivo electroporation. These reporters were observed to label morphologically distinct sets of amacrine cells at the different timepoints harvested in this study. Electroporated retinas were then dissociated at different time points and single retinal amacrine cells were isolated by virtue of their GFP expression and placed in tubes containing lysis buffer. Then, their mRNAs were reverse transcribed, and the resulting cDNAs were PCR amplified for 35 cycles. Labeled cDNA samples were hybridized to Affymetrix 430 2.0 microarrays and the data was normalized using MAS5.0 software.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets