scholarly journals Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Quirino Attilio Vassalli ◽  
Chiara Colantuono ◽  
Valeria Nittoli ◽  
Anna Ferraioli ◽  
Giulia Fasano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Formation ◽  
Transcriptome Profiling ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Progressive Increase ◽  
Retinal Cell ◽  
Genetic Mechanisms ◽  
Core Components ◽  
Multicellular Organisms

Photoreceptor cells (PRC) are neurons highly specialized for sensing light stimuli and have considerably diversified during evolution. The genetic mechanisms that underlie photoreceptor differentiation and accompanied the progressive increase in complexity and diversification of this sensory cell type are a matter of great interest in the field. A role of the homeodomain transcription factor Onecut (Oc) in photoreceptor cell formation is proposed throughout multicellular organisms. However, knowledge of the identity of the Oc downstream-acting factors that mediate specific tasks in the differentiation of the PRC remains limited. Here, we used transgenic perturbation of the Ciona robusta Oc protein to show its requirement for ciliary PRC differentiation. Then, transcriptome profiling between the trans-activation and trans-repression Oc phenotypes identified differentially expressed genes that are enriched in exocytosis, calcium homeostasis, and neurotransmission. Finally, comparison of RNA-Seq datasets in Ciona and mouse identifies a set of Oc downstream genes conserved between tunicates and vertebrates. The transcription factor Oc emerges as a key regulator of neurotransmission in retinal cell types.

scholarly journals Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qingnan Liang ◽  
Rachayata Dharmat ◽  
Leah Owen ◽  
Akbar Shakoor ◽  
Yumei Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Retinal Cell ◽  
Peripheral Retina ◽  
Marker Genes ◽  
Rna Seq ◽  
Cell Type ◽  
Retinal Tissue ◽  
The Individual

AbstractSingle-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an improved power for prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrate that obtaining single cell transcriptomes from human frozen tissues can provide insight missed by either human bulk RNA-seq or animal models.

scholarly journals Islet-1 Immunoreactivity in the Developing Retina ofXenopus laevis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Guadalupe Álvarez-Hernán ◽  
Ruth Bejarano-Escobar ◽  
Ruth Morona ◽  
Agustín González ◽  
Gervasio Martín-Partido ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ganglion Cells ◽  
Temporal Distribution ◽  
Cell Types ◽  
Horizontal Cells ◽  
Retinal Cell ◽  
Spatial And Temporal Distribution ◽  
Cell Nuclei ◽  
Cell Specification ◽  
Islet 1

The LIM-homeodomain transcription factor Islet1 (Isl1) has been widely used as a marker of neuronal differentiation in the developing visual system of different classes of vertebrates, including mammals, birds, reptiles, and fish. In the present study, we analyzed the spatial and temporal distribution of Isl1-immunoreactive cells duringXenopus laevisretinal development and its relation to the formation of the retinal layers, and in combination with different markers of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the cell nuclei of sparse differentiating neuroblasts located in the vitreal surface of the undifferentiated retina. At St35-36, abundant Isl1-positive cells accumulated at the vitreal surface of the neuroepithelium. As development proceeded and through the postmetamorphic juveniles, Isl1 expression was identified in subpopulations of ganglion cells and in subsets of amacrine, bipolar, and horizontal cells. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different retinal cell types, and Isl1 can serve as a specific molecular marker for the study of retinal cell specification inX. laevis.

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 Ultrastructural Circuitry in Retinal Cell Transplants to Rat Retina

1994 ◽  
Vol 5 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Charles L. Zucker ◽  
Berndt Ehinger ◽  
Magdalene Seiler ◽  
Robert B. Aramant ◽  
Alan R. Adolph
Keyword(s):  
Bipolar Cell ◽  
Visual Information ◽  
Pigment Epithelium ◽  
Plexiform Layer ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Inner Plexiform Layer ◽  
Cell Transplants ◽  
Normal Differentiation

The development of five transplants of fetal retinal tissue to adult rat eyes was examined with the electron microscope. The transplants were of 9 to 10 weeks total age after conception in four cases and 20 weeks in one case. They were at stage E15 when transplanted. Transplants developed in both the epiretinal and subretinal spaces.The transplants were heterogeneously developed with some parts showing almost normal differentiation and others little. Subretinal transplants examined in this study were more developed than epiretinal grafts. Photoreceptor cells developed both inner and outer segments. Their synaptic terminals possessed output ribbon synapses with postsynaptic processes similar to those seen in normal retinas. In regions corresponding to the inner plexiform layer, the adult complement of synapses was seen, including advanced features such as serial synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed, especially in the rat epiretinal transplants. Ganglion cell processes could not be identified with certainty.Although transplant cells were adjacent to host photoreceptor cells and pigment epithelium, obvious specializations or interactions were not observed. The experiments suggest that embryonic rat retinal cell transplants develop most or perhaps all of the structural components and neuronal circuitry necessary to transduce light and process some visual information.

scholarly journals Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yevgeniya Atiskova ◽  
Susanne Bartsch ◽  
Tatyana Danyukova ◽  
Elke Becker ◽  
Christian Hagel ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Lysosomal Enzyme ◽  
Ganglion Cells ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Significant Loss ◽  
Retinal Cell ◽  
Depth Analysis ◽  
Palmitoyl Protein Thioesterase

Abstract Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients suffer from brain atrophy, mental and motor retardation, seizures, and retinal degeneration ultimately resulting in blindness. Here, we performed an in-depth analysis of the retinal phenotype of a PPT1-deficient mouse, an animal model of this condition. Reactive astrogliosis and microgliosis were evident in mutant retinas prior to the onset of retinal cell loss. Progressive accumulation of storage material, a pronounced dysregulation of various lysosomal proteins, and accumulation of sequestosome/p62-positive aggregates in the inner nuclear layer also preceded retinal degeneration. At advanced stages of the disease, the mutant retina was characterized by a significant loss of ganglion cells, rod and cone photoreceptor cells, and rod and cone bipolar cells. Results demonstrate that PPT1 dysfunction results in early-onset pathological alterations in the mutant retina, followed by a progressive degeneration of various retinal cell types at relatively late stages of the disease. Data will serve as a reference for future work aimed at developing therapeutic strategies for the treatment of retinal degeneration in CLN1 disease.

scholarly journals Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments

Abstract Background Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. Methods The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2′-deoxyuridine labeling, co-immunoprecipitation, and acyl–biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types. Results Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate. Conclusions Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

scholarly journals Regulation of retinal amacrine cell generation by miR-216b and Foxn3

Development ◽  
2021 ◽  
Author(s):  
Huanqing Zhang ◽  
Pei Zhuang ◽  
Ryan M. Welchko ◽  
Manhong Dai ◽  
Fan Meng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amacrine Cell ◽  
Ectopic Expression ◽  
Cell Formation ◽  
Complex Mixture ◽  
Amacrine Cells ◽  
Retinal Cell ◽  
Mouse Retina ◽  
Different Types ◽  
Retinal Explants

The mammalian retina contains a complex mixture of different types of neurons. We find that microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b directed the formation of additional amacrine cells and reduced bipolar neurons in the developing retina. We identify the Foxn3 mRNA as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3, a transcription factor, in the postnatal developing retina by RNAi increased the formation of amacrine cells and reduced bipolar cell formation. Foxn3 disruption by CRISPR in embryonic retinal explants also increased amacrine cell formation, while Foxn3 overexpression inhibited amacrine cell formation prior to Ptf1a expression. Co-expression of Foxn3 partially reversed the effects of ectopic miR-216b on retinal cell formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates Foxn3 and other genes in amacrine cells.

Propofol Impairs Specification of Retinal Cell Types in Zebrafish by Inhibiting Zisp-mediated Noggin-1 Palmitoylation and Trafficking

2020 ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments ◽  
Developing Neurons

Abstract Background: Propofol can have adverse effects on developing neurons, leading to cognitive disorders. However, the mechanism remains elusive. Here, we aimed to investigate the effect and molecular mechanism of propofol on neuronal development in zebrafish. Methods: The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, Whole-mount in situ hybridization and immunohistochemistry, quantitative real-time PCR, TUNEL, EdU, Co-Immunoprecipitation and acyl–biotin exchange (ABE) labeling method were carried out to demonstrate the potential mechanisms of propofol-mediated zisp expression and specification of retinal cell types.Results: Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through inhibition of Zisp expression. Furthermore, Zisp promoted the secretion of a soluble form and the stabilization of a membrane-associated form of Noggin-1, a specific palmitoylation substrate.Conclusions: Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

scholarly journals Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program

2016 ◽  
Vol 113 (44) ◽  
pp. 12478-12483 ◽  
Author(s):  
Cody Kime ◽  
Masayo Sakaki-Yumoto ◽  
Leeanne Goodrich ◽  
Yohei Hayashi ◽  
Salma Sami ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Cell Types ◽  
Bmp Signaling ◽  
Lipid Signaling ◽  
Downstream Effector ◽  
Morphogenetic Protein ◽  
Multicellular Organisms ◽  
Pr Domain ◽  
Transcription 3

Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion. BMP4, which also stimulates conversion to naive pluripotency, bypassed the need for exogenous LPA by increasing the activity of the extracellular LPA-producing enzyme autotaxin (ATX). We found that LIF and LPA-LPAR1 signaling affect the abundance of signal transducer and activator of transcription 3 (STAT3), which induces a previously unappreciated Kruppel-like factor (KLF)2-KLF4-PR domain 14 (PRDM14) transcription factor circuit key to establish naive pluripotency. AA also affects this transcription factor circuit by controlling PRDM14 expression. Thus, our study reveals that ATX-mediated autocrine lipid signaling promotes naive pluripotency by intersecting with LIF and BMP4 signaling.

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