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Transcriptomic profile of the retinal ganglion cell type J-RGC in Tbr1 KO and control mice

ABSTRACT: The goal of this experiment is to identify genes with altered expression in Tbr1 mutant J-RGCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE108789 | GEO | 2018/04/09

REPOSITORIES: GEO

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Transcriptomic profile of the retinal ganglion cell type J-RGC in Tbr1 KO and control mice

Project description:Transcriptomic profile of the retinal ganglion cell type J-RGC in Tbr1 KO and control mice

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Transcriptomic profile of the retinal ganglion cell type J-RGC

Project description:The goal of this experiment was to identify markers and potential regulators of J-RGC development.

2018-04-09 | GSE102888 | GEO

Shtn1, a retinal ganglion cell (RGC) specific gene, regulates RGC neurite development: Insights from an RGC direct somatic cell reprogramming model

Project description:Retinal ganglion cells (RGCs) are the projection neurons of the retina. Proper development of the axon and dendrite of RGCs is the basis for these cells to function as projection neurons to deliver visual information to the brain. The purpose of this study was to investigate the function of a newly identified RGC-specific gene, Shtn1, in neurite development in RGCs. Using IF, we demonstrated that SHTN1 is distinctively expressed in RGCs during the period in which RGCs actively develop and adjust the connections of their neurites with upstream and downstream neurons. Using the iRGC system, we demonstrated that Shtn1 promotes the growth and complexity of neurites, and thus the electrophysiological maturation, of iRGCs. RNA-Seq analyses showed that Shtn1 may also regulate gene expression and neurogenesis in iRGCs. These findings improve our understanding of the molecular machinery governing RGC neurite development, and may help to optimize future RGC regeneration methods.

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Whole brain transcriptomic analysis of Tbr1-K228E mutant mice

Project description:Mutations of Tbr1, a high-confidence ASD (autism spectrum disorder)-risk gene encoding the transcription regulator TBR1, in mice have been shown to induce diverse ASD-related molecular, synaptic, neuronal, and behavioral dysfunctions. However, it remains unclear whether Tbr1 mutations derived from autistic individuals cause similar dysfunctions in mice remains unclear. Here we generated and characterized mice carrying the TBR1-K228E de novo mutation identified in human ASD and identified various ASD-related phenotypes. In heterozygous mice carrying this mutation (Tbr1+/K228E mice), the levels of the TBR1-K228E protein, which cannot bind to target DNA, were strongly increased. RNA-Seq analysis of the Tbr1+/K228E embryonic brain indicated significant changes in the expression of genes associated with neurons, astrocytes, ribosomes, neuronal synapses, and ASD risk. The Tbr1+/K228E neocortex displayed abnormal distribution of parvalbumin-positive interneurons, with the density lower in superficial layers but higher in deep layers. This was associated with increased inhibitory synaptic transmission in layer 6 pyramidal neurons, which was resistant to compensation by network activity. Behaviorally, Tbr1+/K228E mice showed decreased social interaction, increased self-grooming, and modestly increased anxiety-like behaviors. These results suggest that the human heterozygous TBR1-K228E mutation induces ASD-related protein, transcriptomic, neuronal, synaptic, and behavioral dysfunctions in mice.

2019-09-29 | GSE134526 | GEO

Genetic signatures of retinal ganglion cells revealed through single cell profiling [dissociated RGC]

Project description:This study aimed to characterize the transcriptomes of adult retinal ganglion cells (RGCs). These cells were isolated through their expression of a TdTomato molecule that would only turn on when Cre was present. Cre was controlled by the Parvalbumin promoter.

2019-11-01 | GSE115332 | GEO

Genetic signatures of retinal ganglion cells revealed through single cell profiling [non-dissociated RGC]

Project description:This study aimed to characterize the transcriptomes of adult retinal ganglion cells (RGCs). The physiological properties of these cells were characterized first in non-dissociated retinal tissue. With that information recorded, the cells were isolated for transcriptome profiling.

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single-nucleus RNA-seq of enriched retinal ganglion cells (RGCs) with RGC-specific overexpression of hOprm1 under optic nerve crush injury condition

Project description:Through a comparative analysis of RGC subclasses exhibiting varying levels of resilience to cell death, based on cell-cell interaction analysis, we identified the Mu-opioid receptor, encoded by the Oprm1 gene, as a novel neuroprotective factor for pan-RGCs. Functionally and with the sequencing dataset deposited here, we validated Oprm1 as a neuroprotective factor for RGCs, by demonstrating that overexpression of Oprm1 in RGCs not only led to a markedly increased survival rate of RGCs following several different types of retinal injuries, but also significantly improved visually-guided perception behaviors.

2023-12-26 | GSE248537 | GEO

Tbr1 instructs laminar patterning of retinal ganglion cell dendrites.

Project description:Visual information is delivered to the brain by >40 types of retinal ganglion cells (RGCs). Diversity in this representation arises within the inner plexiform layer (IPL), where dendrites of each RGC type are restricted to specific sublaminae, limiting the interneuronal types that can innervate them. How such dendritic restriction arises is unclear. We show that the transcription factor Tbr1 is expressed by four mouse RGC types with dendrites in the outer IPL and is required for their laminar specification. Loss of Tbr1 results in elaboration of dendrites within the inner IPL, while misexpression in other cells retargets their neurites to the outer IPL. Two transmembrane molecules, Sorcs3 and Cdh8, act as effectors of the Tbr1-controlled lamination program. However, they are expressed in just one Tbr1+ RGC type, supporting a model in which a single transcription factor implements similar laminar choices in distinct cell types by recruiting partially non-overlapping effectors.

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Analysis of TBR1 downnstream target genes in embryonic forebrains

Project description:TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala. To investigate how TBR1 regulates neural development, the gene expression profile of Tbr1-/- brains was compared with WT littermates. Total RNAs purified from forebrains at embryonic day 16.5 were hybridized on Affymetrix microarrays

2013-12-31 | E-GEOD-49237 | biostudies-arrayexpress

Analysis of TBR1 downnstream target genes in embryonic forebrains

2013-12-31 | GSE49237 | GEO