scholarly journals Functional analysis of Samd11, a retinal photoreceptor PRC1 component, in establishing rod photoreceptor identity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shun Kubo ◽  
Haruka Yamamoto ◽  
Naoko Kajimura ◽  
Yoshihiro Omori ◽  
Yamato Maeda ◽  
...  
Keyword(s):  
Neuronal Cell ◽  
Photoreceptor Cells ◽  
Retinal Cell ◽  
Neural Function ◽  
Rod Photoreceptor ◽  
Cell Identity ◽  
Knock Out ◽  
Sam Domain ◽  
Accessory Factor ◽  
Domain Protein

AbstractEstablishing correct neuronal cell identity is essential to build intricate neural tissue architecture and acquire precise neural function during vertebrate development. While it is known that transcription factors play important roles in retinal cell differentiation, the contribution of epigenetic factors to establishing cell identity during retinal development remains unclear. We previously reported that Samd7, a rod photoreceptor cell-specific sterile alpha motif (SAM) domain protein, functions as a Polycomb repressive complex 1 component (PRC1) that is essential for establishing rod identity. In the current study, we analyzed a functional role of Samd11, another photoreceptor-enriched SAM-domain protein, in photoreceptor differentiation and maturation. We observed that Samd11 interacts with Phc2 and Samd7, suggesting that Samd11 is a component of PRC1 in photoreceptor cells. We generated Samd11-null allele and established Samd7/11 double knock-out (DKO) mouse. The Samd7/11 DKO retina exhibits shortened photoreceptor outer segments by electron microscopy analysis. Microarray analysis revealed that Samd7/11 DKO up-regulated more retinal genes than Samd7−/− alone, partial functional redundancy of Samd7 and Samd11. Taken together, the current results suggest that Samd7 and Samd11 are PRC1 components and that Samd7 is the major regulator while Samd11 is an accessory factor used for the establishment of precise rod photoreceptor identity.

Expression profiling of GABAA receptor β-subunits in the rat retina

1994 ◽  
Vol 11 (2) ◽  
pp. 379-387 ◽  
Author(s):  
Elena V. Grigorenko ◽  
Hermes H. Yeh
Keyword(s):  
Ganglion Cells ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Bipolar Cells ◽  
Retinal Cell ◽  
Rod Photoreceptor ◽  
Β Subunit ◽  
Rt Pcr ◽  
Retinal Neuron ◽  
Rat Retina

AbstractThis study profiled the expression of the family of GABAA receptor β-subunits in the adult rat retina. Using a combination of reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR) with gene-specific primers, the expression of mRNAs encoding the β1, β2, and β3 subunits was first examined in the intact retina and then in separated retinal nuclear layers. However, it was found that a critical analysis. had to be carried out at the level of the single cell in order to resolve the differential patterns of expression among the retinal cell types. When cells were isolated and identified following acute dissociation, RT-PCR revealed that individual rod photoreceptor cells expressed consistently the β1 and β2 messages while the bipolar cells expressed the β1 and β3 messages. Ganglion cells displayed considerable variability in β-subunit expression, perhaps reflecting their functional and morphological heterogeneity in the retina. In contrast, the nonneuronal Mueller cells did not express any of the β-subunit messages. These results indicate that the expression of GABAA receptor subunits is cell-type dependent. Furthermore, as the expression of other families of GABAA receptor subunits are profiled and the patterns of subunit assembly are better understood, our results raise the possibility that GABAA receptors with different subunit compositions can be expected to be coexpressed within a single retinal neuron.

scholarly journals Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity

2017 ◽  
Vol 114 (39) ◽  
pp. E8264-E8273 ◽  
Author(s):  
Yoshihiro Omori ◽  
Shun Kubo ◽  
Tetsuo Kon ◽  
Mayu Furuhashi ◽  
Hirotaka Narita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Photoreceptor Cell ◽  
Ectopic Expression ◽  
Neuronal Cell ◽  
Photoreceptor Cells ◽  
Rod Photoreceptor ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Null Mutant Mice

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7-null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7-deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

Ayurvedic management of Retinitis Pigmentosa (Doshandha) - A Case Study

2017 ◽  
Vol 2 (05) ◽  
Author(s):  
Anju D. ◽  
Pushpa Raj Poudel ◽  
Ajoy Viswam ◽  
Ashwini M. J.
Keyword(s):  
Retinitis Pigmentosa ◽  
Low Vision ◽  
Symptomatic Relief ◽  
Retinal Dystrophy ◽  
Treatment Protocol ◽  
Signs And Symptoms ◽  
Photoreceptor Cells ◽  
Rod Photoreceptor ◽  
Night Time ◽  
Initial Symptoms

Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment due to the progressive degeneration of rod photoreceptor cells in retina. This form of retinal dystrophy manifests initial symptoms independentof age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. This primary pigmentary retinal dystrophy is a hereditary disorder predominantly affecting the rods more than the cones. The main classical triads of retinitis pigmentosa are arteriolar attenuation, Retinal bone spicule pigmentation and Waxy disc pallor. The main treatment of retinitis pigmentosa is by using Low vision aids (LVA) and Genetic counseling. As such a complete cure for retinitis pigmentosa is not present. So a treatment protocol has to be adopted that helps in at least the symptomatic relief. In Ayurveda, the signs and symptoms of this can be compared with the Lakshanas of Doshandha which is one among the Dristigata Roga. It is considered as a diseased condition in which sunset will obliterate the Dristi Mandala and makes the person blind at night time. During morning hours the rising sunrays will disperse the accumulated Dosas from Dristi to clear vision. This disease resembles Kaphajatimira in its pathogenesis, but the night blindness is the special feature. Since the disease is purely Kaphaja, a treatment attempt is planned in Kaphara and Brimhana line. The present paper discusses a case of retinitis pigmentosa and it’s Ayurvedic Treatment.

scholarly journals Attenuation of inhibitory PAS domain protein-induced cell death by synthetic peptides derived from Mcl-1 transmenbrane domain

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuya Kasai ◽  
Ken-ichi Yasumoto ◽  
Kazuhiro Sogawa
Keyword(s):  
Cell Death ◽  
Synthetic Peptides ◽  
Specific Binding ◽  
Neuronal Cell ◽  
Chimeric Protein ◽  
Substantia Nigra Pars Compacta ◽  
Pas Domain ◽  
Domain Protein ◽  
Tm Domain ◽  
Apoptotic Activity

AbstractExpression of Inhibitory PAS domain protein (IPAS) induces apoptosis by inhibiting the anti-apoptotic activity of mitochondrial pro-survival proteins including Bcl-xL and Mcl-1 through direct binding. Analysis to examine the IPAS-binding region in Bcl-xL demonstrated that the C-terminal transmembrane (TM) domain is indispensable for the specific binding. A chimeric protein composed of the TM domain of Mcl-1 fused to the C-terminus of Citrine also exhibited a binding affinity to IPAS, and markedly attenuated apoptosis caused by the overexpression of Cerulean-IPAS in SH-SY5Y cells. HIV-1 TAT cell-penetrating peptide-conjugated synthetic peptides that cover whole or parts of the Mcl-1 TM domain showed anti-apoptotic activity in the CoCl2-induced cell death in PC12 cells. Administration of these highly effective anti-apoptotic peptides to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that produces a reliable mouse model of Parkinson’s disease (PD) decreased neuronal cell loss in the substantia nigra pars compacta. Therefore, the peptides may be considered promising therapeutic agents for neurodegenerative disorders such as PD and stroke.

scholarly journals Cell type resolved co-expression networks of core clock genes in brain development

2021 ◽  
Author(s):  
Surbhi Sharma ◽  
Asgar Hussain Ansari ◽  
Soundhar Ramasamy
Keyword(s):  
Circadian Clock ◽  
Single Cell ◽  
Radial Glia ◽  
Clock Genes ◽  
Neuronal Cell ◽  
Cell Types ◽  
Developing Brain ◽  
Knock Out

AbstractThe circadian clock regulates vital cellular processes by adjusting the physiology of the organism to daily changes in the environment. Rhythmic transcription of core Clock Genes (CGs) and their targets regulate these processes at the cellular level. Circadian clock disruption has been observed in people with neurodegenerative disorders like Alzheimer’s and Parkinson’s. Also, ablation of CGs during development has been shown to affect neurogenesis in both in vivo and in vitro models. Previous studies on the function of CGs in the brain have used knock-out models of a few CGs. However, a complete catalog of CGs in different cell types of the developing brain is not available and it is also tedious to obtain. Recent advancements in single-cell RNA sequencing (scRNA-seq) has revealed novel cell types and elusive dynamic cell states of the developing brain. In this study by using publicly available single-cell transcriptome datasets we systematically explored CGs-coexpressing networks (CGs-CNs) during embryonic and adult neurogenesis. Our meta-analysis reveals CGs-CNs in human embryonic radial glia, neurons and also in lesser studied non-neuronal cell types of the developing brain.

scholarly journals Glycolytic reliance promotes anabolism in photoreceptors

2017 ◽  
Author(s):  
Yashodhan Chinchore ◽  
Tedi Begaj ◽  
David Wu ◽  
Eugene Drokhlyansky ◽  
Constance L. Cepko
Keyword(s):  
Outer Segment ◽  
Atp Hydrolysis ◽  
Carbon Allocation ◽  
Aerobic Glycolysis ◽  
Neuronal Cell ◽  
Photoreceptor Cells ◽  
Glycolytic Pathway ◽  
Membrane Excitability ◽  
Proliferating Cells ◽  
Genetic Perturbations

Sensory neurons capture information from the environment and convert it into signals that can greatly impact the survival of an organism. These systems are thus under heavy selective pressure, including for the most efficient use of energy to support their sensitivity and efficiency1. In this regard, the vertebrate photoreceptor cells face a dual challenge. They not only need to preserve their membrane excitability via ion pumps by ATP hydrolysis2 but also maintain a highly membrane rich organelle, the outer segment, which is the primary site of phototransduction, creating a considerable biosynthetic demand. How photoreceptors manage carbon allocation to balance their catabolic and anabolic demands is poorly understood. One metabolic feature of the retina is its ability to convert the majority of its glucose into lactate3,4 even in the presence of oxygen. This phenomenon, aerobic glycolysis, is found in cancer and proliferating cells, and is thought to promote biomass buildup to sustain proliferation5,6. The purpose of aerobic glycolysis in the retina, its relevance to photoreceptor physiology, and its regulation, are not understood. Here, we show that rod photoreceptors rely on glycolysis for their outer segment (OS) biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the OS size. Fibroblast growth factor (FGF) signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in OS maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type.

scholarly journals Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell function and fate

2018 ◽  
Vol 475 (15) ◽  
pp. 2511-2545 ◽  
Author(s):  
Anthony J. Hayes ◽  
James Melrose
Keyword(s):  
Cell Fate ◽  
Information Transfer ◽  
Cell Function ◽  
Dermatan Sulfate ◽  
Neuronal Cell ◽  
Keratan Sulfate ◽  
Neural Function ◽  
Cellular Survival ◽  
Downstream Signaling ◽  
Blood Group Substances

The aim of the present study was to examine the roles of l-fucose and the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan sulfate (CS/DS) with selected functional molecules in neural tissues. Cell surface glycans and GAGs have evolved over millions of years to become cellular mediators which regulate fundamental aspects of cellular survival. The glycocalyx, which surrounds all cells, actuates responses to growth factors, cytokines and morphogens at the cellular boundary, silencing or activating downstream signaling pathways and gene expression. In this review, we have focused on interactions mediated by l-fucose, KS and CS/DS in the central and peripheral nervous systems. Fucose makes critical contributions in the area of molecular recognition and information transfer in the blood group substances, cytotoxic immunoglobulins, cell fate-mediated Notch-1 interactions, regulation of selectin-mediated neutrophil extravasation in innate immunity and CD-34-mediated new blood vessel development, and the targeting of neuroprogenitor cells to damaged neural tissue. Fucosylated glycoproteins regulate delivery of synaptic neurotransmitters and neural function. Neural KS proteoglycans (PGs) were examined in terms of cellular regulation and their interactive properties with neuroregulatory molecules. The paradoxical properties of CS/DS isomers decorating matrix and transmembrane PGs and the positive and negative regulatory cues they provide to neurons are also discussed.

scholarly journals Human iPS Cell-Derived Patient Tissues and 3D Cell Culture Part 2: Spheroids, Organoids, and Disease Modeling

2019 ◽  
Vol 24 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Richard M. Eglen ◽  
Terry Reisine
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Disease Modeling ◽  
Cortical Cell ◽  
Neuronal Cell ◽  
3D Cell Culture ◽  
Retinal Cell ◽  
Major Advance ◽  
Ips Cell ◽  
Culture Systems

Human induced pluripotent stem cells (HiPSCs) provide several advantages for drug discovery, but principally they provide a source of clinically relevant tissue. Furthermore, the use of HiPSCs cultured in three-dimensional (3D) systems, as opposed to traditional two-dimensional (2D) culture approaches, better represents the complex tissue architecture in vivo. The use of HiPSCs in 3D spheroid and organoid culture is now growing, but particularly when using myocardial, intestinal enteric nervous system, and retinal cell lines. However, organoid cell culture is perhaps making the most notable impact in research and drug discovery, in which 3D neuronal cell cultures allow direct modeling of cortical cell layering and neuronal circuit activity. Given the specific degeneration seen in discrete neuronal circuitry in Alzheimer’s disease (AD) and Parkinson’s disease (PD), HiPSC culture systems are proving to be a major advance. In the present review, the second part of a two-part review, we discuss novel methods in which 3D cell culture systems (principally organoids) are now being used to provide insights into disease mechanisms. (The use of HiPSCs in target identification was reviewed in detail in Part 1.)

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