Feedback Induction of a Photoreceptor-specific Isoform of Retinoid-related Orphan Nuclear Receptor β by the Rod Transcription Factor NRL

Fu, Yulong; Liu, Hong; Ng, Lily; Kim, Jung-Woong; Hong, Huasheng; Swaroop, Anand; Forrest, Douglas

doi:10.1074/jbc.m114.605774

Cited by 25 publications

(31 citation statements)

References 53 publications

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“…The overall sequences of Rorβ1 and Rorβ2 are identical except for short, unique 5′ exons (Liu et al, ), such that our in situ probe detects mRNA for both Rorβ1 and Rorβ2 isoforms. The biochemical properties of Rorβ1 and Rorβ2 are similar in transcriptional activation (Fu et al, ). By using knockin reporter mice, strong signals were detected in the sSC in the Rorβ 1g/+ strain but not in the Rorβ 2z/+ strain.…”

Section: Methodsmentioning

confidence: 99%

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus

Byun

Kwon

Ahn

et al. 2016

J of Comparative Neurology

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The superior colliculus (SC) is a midbrain center involved in controlling head and eye movements in response to inputs from multiple sensory modalities. Visual inputs arise from both the retina and visual cortex and converge onto the superficial layer of the SC (sSC). Neurons in sSC send information to deeper layers of SC and to thalamic nuclei that modulate visually guided behaviors. Presently, our understanding of sSC neurons is impeded by a lack of molecular markers that define specific cell types. To better understand the identity and organization of sSC neurons, we took a systematic approach to investigate gene expression within four molecular families: transcription factors, cell adhesion molecules, neuropeptides and calcium binding proteins. Our analysis revealed 12 molecules with distinct expression patterns in mouse sSC: cadherin 7, contactin 3, netrin G2, cadherin 6, protocadherin 20, retinoid-related orphan receptor β, brain-specific homeobox/POU domain protein 3b, Ets variant gene 1, substance P, somatostatin, vasoactive intestinal polypeptide and parvalbumin. Double labeling experiments, by either in situ hybridization or immunostaining, demonstrated that the 12 molecular markers collectively define 10 different sSC neuronal types. The characteristic positions of these cell types divide sSC into 4 distinct layers. The 12 markers identified here will serve as valuable tools to examine molecular mechanisms that regulate development of sSC neuron types. These markers could also be used to examine the connections between specific cell types that form retinocollicular, corticocollicular or colliculothalamic pathways.

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Section: Methodsmentioning

confidence: 99%

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus

Byun

Kwon

Ahn

et al. 2016

J of Comparative Neurology

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“…Recent insights have come from characterizing other transcription factors expressed in retinal progenitors. For example, the transcription factors Foxn4 and Rorβ are expressed by progenitors (Chow et al, 1998;Li et al, 2004;Luo et al, 2012;Liu et al, 2013;Fu et al, 2014) and combine to induce the expression of Ptf1a, which encodes a transcription factor that is necessary for amacrine and horizontal cell genesis (Fujitani et al, 2006;Liu et al, 2013). Lineage tracing of Ptf1a-expressing cells labels only horizontal and amacrine cells (Fujitani et al, 2006), suggesting that any Otx2-expressing cells that also express Ptf1a have already (or will) become restricted to these two fates.…”

Section: Box 2 Photoreceptor Loss and Dysfunctionmentioning

confidence: 99%

“…Otx2 and Rorβ are needed to initiate the expression of the transcription factor Nrl in a subpopulation of newly postmitotic precursors: these Nrl-expressing cells will develop into rod photoreceptors (Fig. 3C) Kautzmann et al, 2011;Fu et al, 2014;Roger et al, 2014). Without either Rorb or Nrl, rod photoreceptor cells do not develop; instead, there is an approximately one-to-one fate shift to S-opsin-expressing cone cells (Mears et al, 2001;Fu et al, 2014).…”

Section: Transcriptional Network Regulating Photoreceptor Identitymentioning

confidence: 99%

“…3C) Kautzmann et al, 2011;Fu et al, 2014;Roger et al, 2014). Without either Rorb or Nrl, rod photoreceptor cells do not develop; instead, there is an approximately one-to-one fate shift to S-opsin-expressing cone cells (Mears et al, 2001;Fu et al, 2014). Nrl is needed to activate several essential rod-specific genes, including Nr2e3, a transcription factor that can both co-activate rod genes and silence cone genes, such as Opn1sw (S-opsin) (Fig.…”

Section: Transcriptional Network Regulating Photoreceptor Identitymentioning

confidence: 99%

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Photoreceptor cell fate specification in vertebrates

2015

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Photoreceptors -the light-sensitive cells in the vertebrate retinahave been extremely well-characterized with regards to their biochemistry, cell biology and physiology. They therefore provide an excellent model for exploring the factors and mechanisms that drive neural progenitors into a differentiated cell fate in the nervous system. As a result, great progress in understanding the transcriptional network that controls photoreceptor specification and differentiation has been made over the last 20 years. This progress has also enabled the production of photoreceptors from pluripotent stem cells, thereby aiding the development of regenerative medical approaches to eye disease. In this Review, we outline the signaling and transcription factors that drive vertebrate photoreceptor development and discuss how these function together in gene regulatory networks to control photoreceptor cell fate specification.

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“…The neural retina leucine zipper transcription factor NRL is essential for rod photoreceptor development [48]. The activation of rod genes in cone-like precursors depends on the induction of NRL [49].…”

Section: Discussionmentioning

confidence: 99%

A quantitative transcriptomic analysis of the physiological significance of mTOR signaling in goat fetal fibroblasts

Zheng

Jia

et al. 2016

BMC Genomics

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BackgroundMammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that is a central regulator of cell growth and metabolism. CCI-779 is a specific inhibitor of the mTORC1 signaling pathway.ResultsWe performed comparative transcriptome profiling on Inner Mongolia Cashmere goat fetal fibroblasts (GFbs) that were treated with CCI-779 and untreated cells. A total of 365 differentially expressed genes (DEGs) appeared between untreated and CCI-779-treated GFbs, with an FDR ≤0.001 and fold-change ≥2. These 365 DEGs were associated with mTOR signaling; 144 were upregulated in CCI-779-treated cells, and 221 were downregulated.Additionally, 300 genes were annotated with 43 Gene Ontology (GO) terms, and 293 genes were annotated with 194 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Three RNA polymerase II and polymerase III subunits, 3 transcription factors, and 5 kinases in mTOR signaling were differentially expressed in CCI-779-treated GFbs. Further 6 DEGs were related to amino acid metabolism, 11 mediated lipid metabolism, 11 participated in carbohydrate metabolism, and 5 were involved in single-nucleotide metabolism. Based on our quantitative transcriptomic analysis, 40 significant DEGs with important function related to metabolism, RNA polymerase, transcription factors and mTOR signaling were selected for qPCR analysis, and the quantitative results between the two analysis methods were concordant. The qPCR data confirmed the differential expression in the RNA-Seq experiments. To validate the translational significance of the findings in certain differentially expressed genes, S6K1 and VEGF were detected by western blot, and these two proteins showed a differential expression between non-treated and treated with CCI-779 groups, which were consistent with mRNA abundance. The data showed a preliminary significance of the findings in the protein levels.ConclusionsCCI-779 induces transcriptomic changes, and mTOR signaling might have significant function in the activation of RNA polymerase and certain transcription factors and in the metabolism of amino acids, lipids, carbohydrates, and single nucleotides in GFbs. These data filled the vacancy in the systematical profiling of mTOR signaling on Cashmere goat fetal fibroblasts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3151-y) contains supplementary material, which is available to authorized users.

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Feedback Induction of a Photoreceptor-specific Isoform of Retinoid-related Orphan Nuclear Receptor β by the Rod Transcription Factor NRL

Cited by 25 publications

References 53 publications

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus

Photoreceptor cell fate specification in vertebrates

A quantitative transcriptomic analysis of the physiological significance of mTOR signaling in goat fetal fibroblasts

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