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Otx2

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https://www.readbyqxmd.com/read/29771284/non-cell-autonomous-otx2-homeoprotein-regulates-visual-cortex-plasticity-through-gadd45b-g
#1
Jessica Apulei, Namsuk Kim, Damien Testa, Jérôme Ribot, David Morizet, Clémence Bernard, Laurent Jourdren, Corinne Blugeon, Ariel A Di Nardo, Alain Prochiantz
The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and nonplastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription...
May 16, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29732603/sox2-conditional-mutation-in-mouse-causes-ataxic-symptoms-cerebellar-vermis-hypoplasia-and-postnatal-defects-of-bergmann-glia
#2
Valentina Cerrato, Sara Mercurio, Ketty Leto, Elisa Fucà, Eriola Hoxha, Sara Bottes, Miriam Pagin, Marco Milanese, Chew-Yee Ngan, Giulia Concina, Sergio Ottolenghi, Chia-Lin Wei, Giambattista Bonanno, Giulio Pavesi, Filippo Tempia, Annalisa Buffo, Silvia K Nicolis
Sox2 is a transcription factor active in the nervous system, within different cell types, ranging from radial glia neural stem cells to a few specific types of differentiated glia and neurons. Mutations in the human SOX2 transcription factor gene cause various central nervous system (CNS) abnormalities, involving hippocampus and eye defects, as well as ataxia. Conditional Sox2 mutation in mouse, with different Cre transgenes, previously recapitulated different essential features of the disease, such as hippocampus and eye defects...
May 6, 2018: Glia
https://www.readbyqxmd.com/read/29588463/combining-targeted-panel-based-resequencing-and-copy-number-variation-analysis-for-the-diagnosis-of-inherited-syndromic-retinopathies-and-associated-ciliopathies
#3
Iker Sanchez-Navarro, Luciana R J da Silva, Fiona Blanco-Kelly, Olga Zurita, Noelia Sanchez-Bolivar, Cristina Villaverde, Maria Isabel Lopez-Molina, Blanca Garcia-Sandoval, Saoud Tahsin-Swafiri, Pablo Minguez, Rosa Riveiro-Alvarez, Isabel Lorda, Rocío Sanchez-Alcudia, Raquel Perez-Carro, Diana Valverde, Yichuan Liu, Lifeng Tian, Hakon Hakonarson, Almudena Avila-Fernandez, Marta Corton, Carmen Ayuso
Inherited syndromic retinopathies are a highly heterogeneous group of diseases that involve retinal anomalies and systemic manifestations. They include retinal ciliopathies, other well-defined clinical syndromes presenting with retinal alterations and cases of non-specific multisystemic diseases. The heterogeneity of these conditions makes molecular and clinical characterization of patients challenging in daily clinical practice. We explored the capacity of targeted resequencing and copy-number variation analysis to improve diagnosis of a heterogeneous cohort of 47 patients mainly comprising atypical cases that did not clearly fit a specific clinical diagnosis...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29574166/stem-cells-from-apical-papilla-promote-differentiation-of-human-pluripotent-stem-cells-towards-retinal-cells
#4
Fereshteh Karamali, Mohammad-Hossein Nasr Esfahani, Sara Taleahmad, Leila Satarian, Hossein Baharvand
Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8. Furthermore, the differentiated cells on SCAP significantly expressed eye-field markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies...
March 2, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29548329/chronic-exposure-to-tumor-necrosis-factor-alpha-induces-retinal-pigment-epithelium-cell-dedifferentiation
#5
Sara Touhami, Fanny Beguier, Sébastien Augustin, Hugo Charles-Messance, Lucile Vignaud, Emeline F Nandrot, Sacha Reichman, Valérie Forster, Thibaud Mathis, José-Alain Sahel, Bahram Bodaghi, Xavier Guillonneau, Florian Sennlaub
BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0...
March 16, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29490009/metastatic-group-3-medulloblastoma-is-driven-by-prune1-targeting-nme1-tgf-%C3%AE-otx2-snail-via-pten-inhibition
#6
Veronica Ferrucci, Pasqualino de Antonellis, Francesco Paolo Pennino, Fatemeh Asadzadeh, Antonella Virgilio, Donatella Montanaro, Aldo Galeone, Iolanda Boffa, Ida Pisano, Iolanda Scognamiglio, Luigi Navas, Donatella Diana, Emilia Pedone, Sara Gargiulo, Matteo Gramanzini, Arturo Brunetti, Laura Danielson, Marianeve Carotenuto, Lucia Liguori, Antonio Verrico, Lucia Quaglietta, Maria Elena Errico, Valentina Del Monaco, Valeria D'Argenio, Felice Tirone, Angela Mastronuzzi, Vittoria Donofrio, Felice Giangaspero, Daniel Picard, Marc Remke, Livia Garzia, Craig Daniels, Olivier Delattre, Fredrik J Swartling, William A Weiss, Francesco Salvatore, Roberto Fattorusso, Louis Chesler, Michael D Taylor, Giuseppe Cinalli, Massimo Zollo
Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition...
May 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29467473/embryonic-lethality-in-mice-lacking-trim59-due-to-impaired-gastrulation-development
#7
Xiaomin Su, Chenglei Wu, Xiaoying Ye, Ming Zeng, Zhujun Zhang, Yongzhe Che, Yuan Zhang, Lin Liu, Yushuang Lin, Rongcun Yang
TRIM family members have been implicated in a variety of biological processes such as differentiation and development. We here found that Trim59 plays a critical role in early embryo development from blastocyst stage to gastrula. There existed delayed development and empty yolk sacs from embryonic day (E) 8.5 in Trim59-/- embryos. No viable Trim59-/- embryos were observed beyond E9.5. Trim59 deficiency affected primary germ layer formation at the beginning of gastrulation. At E6.5 and E7.5, the expression of primary germ layer formation-associated genes including Brachyury, lefty2, Cer1, Otx2, Wnt3, and BMP4 was reduced in Trim59-/- embryos...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29461140/genetic-investigation-of-ocular-developmental-genes-in-52-patients-with-anophthalmia-microphthalmia
#8
Nair Gopinathan Vidya, Sankaranarayanan Rajkumar, Abhay R Vasavada
BACKGROUND: Mutation in eye developmental genes has been reported to cause anophthalmia and microphthalmia. However, in India, especially in the Western Indian population, such reports are scarce. Hence, the present study aims to investigate mutations in 15 ocular developmental genes in patients with anophthalmia and microphthalmia in the western region of India. MATERIALS AND METHODS: Genomic DNA was isolated from the blood of 52 individuals affected with microphthalmia and anophthalmia, and 50 healthy normal controls...
June 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/29456495/structural-variation-of-chondroitin-sulfate-chains-contributes-to-the-molecular-heterogeneity-of-perineuronal-nets
#9
Shinji Miyata, Satomi Nadanaka, Michihiro Igarashi, Hiroshi Kitagawa
Aggrecan, a chondroitin sulfate (CS) proteoglycan, forms lattice-like extracellular matrix structures called perineuronal nets (PNNs). Neocortical PNNs primarily ensheath parvalbumin-expressing inhibitory neurons (parvalbumin, PV cells) late in brain development. Emerging evidence indicates that PNNs promote the maturation of PV cells by enhancing the incorporation of homeobox protein Otx2 and regulating experience-dependent neural plasticity. Wisteria floribunda agglutinin (WFA), an N-acetylgalactosamine-specific plant lectin, binds to the CS chains of aggrecan and has been widely used to visualize PNNs...
2018: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29442330/roles-of-zic2-in-regulation-of-pluripotent-stem-cells
#10
Hisato Kondoh
Pioneered by the classical mouse embryonic stem cells (ESCs), various stem cell lines representing the peri- and postimplantation stages of embryogenesis have been established. To gain insight into the gene regulatory network operating in these cells, we first investigated epiblast stem cells (EpiSCs), performing ChIP-seq analysis for five major transcription factors (TFs) involved in epiblast regulation. The analysis indicated that SOX2-POU5F1 TF pairs highlighted in mouse ESCs are not the major players in other stem cells...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29435650/targeted-knock-in-of-creer-t2-in-zebrafish-using-crispr-cas9
#11
Gokul Kesavan, Juliane Hammer, Stefan Hans, Michael Brand
New genome-editing approaches, such as the CRISPR/Cas system, have opened up great opportunities to insert or delete genes at targeted loci and have revolutionized genetics in model organisms like the zebrafish. The Cre-loxp recombination system is widely used to activate or inactivate genes with high spatial and temporal specificity. Using a CRISPR/Cas9-mediated knock-in strategy, we inserted a zebrafish codon-optimized CreER T2 transgene at the otx2 gene locus to generate a conditional Cre-driver line. We chose otx2 as it is a patterning gene of the anterior neural plate that is expressed during early development...
April 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29386354/antagonism-between-the-transcription-factors-nanog-and-otx2-specifies-rostral-or-caudal-cell-fate-during-neural-patterning-transition
#12
Zhenghui Su, Yanqi Zhang, Baojian Liao, Xiaofen Zhong, Xin Chen, Haitao Wang, Yiping Guo, Yongli Shan, Lihui Wang, Guangjin Pan
During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation...
March 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29377567/characterization-of-a-novel-otx2-driven-stem-cell-program-in-group-3-and-group-4-medulloblastoma
#13
Margaret Stromecki, Nazanin Tatari, Ludivine Coudière Morrison, Ravinder Kaur, Jamie Zagozewski, Gareth Palidwor, Vijay Ramaswamy, Patryk Skowron, Matthias Wölfl, Till Milde, Marc R Del Bigio, Michael D Taylor, Tamra E Werbowetski-Ogilvie
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo...
April 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29377330/the-poly-cistronic-expression-of-four-transcriptional-factors-crx-rax-neuro-d-otx2-in-fibroblasts-via-retro-or-lentivirus-causes-partial-reprogramming-into-photoreceptor-cells
#14
Tomokazu Fukuda, Yasushi Ishizawa, Kenichiro Donai, Eriko Sugano, Hiroshi Tomita
The introduction of four key transcriptional factors (CRX, RAX, NEURO-D, OTX2) allows the direct differentiation of fibroblasts to retinal photoreceptor cells. This reprogramming was achieved with a combination of mono-cistronic viruses. Although the combination of mono-cistronic viruses was useful, a relatively high titer of recombinant viruses was necessary because co-infections are required. To overcome this issue, we established a poly-cistronic expression system for direct reprogramming and analyzed the biological characteristics of introduced cells after the exogenous introduction...
May 2018: Cell Biology International
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#15
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+ , tau+/- , tau-/- mice. We found tau deficiency could not induce significant motor disorders...
March 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29204067/heterozygous-mutation-in-otx2-associated-with-early-onset-retinal-dystrophy-with-atypical-maculopathy
#16
Maram Ea Abdalla-Elsayed, Patrik Schatz, Christine Neuhaus, Arif O Khan
Purpose: Heterozygous mutations in OTX2 have been associated with a range of ocular and pituitary abnormalities. We report a novel heterozygous deletion in OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Methods: Clinical examination included electroretinography and multimodal retinal imaging. Molecular genetic testing was composed of next-generation sequencing of a panel of retinal dystrophy genes. Results: A now 17-year-old boy presented 12 years earlier with a history of progressively poor vision since birth, nyctalopia, and early-onset retinal dystrophy with atypical maculopathy...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29178648/panel-based-whole-exome-sequencing-identifies-novel-mutations-in-microphthalmia-and-anophthalmia-patients-showing-complex-mendelian-inheritance-patterns
#17
Marina Riera, Ana Wert, Isabel Nieto, Esther Pomares
BACKGROUND: Microphthalmia and anophthalmia (MA) are congenital eye abnormalities that show an extremely high clinical and genetic complexity. In this study, we evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of MA patients. This approach was used to investigate three unrelated families in which previous single-gene analyses failed to identify the molecular cause. METHODS: A total of 47 genes previously associated with nonsyndromic MA were included in our panel...
November 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29147115/effects-of-aminoglycoside-antibiotics-on-human-embryonic-stem-cell-viability-during-differentiation-in-vitro
#18
Divya S Varghese, Shama Parween, Mustafa T Ardah, Bright Starling Emerald, Suraiya A Ansari
Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29056334/functional-antagonism-between-otx2-and-nanog-specifies-a-spectrum-of-heterogeneous-identities-in-embryonic-stem-cells
#19
Dario Acampora, Luca Giovanni Di Giovannantonio, Arcomaria Garofalo, Vincenzo Nigro, Daniela Omodei, Alessia Lombardi, Jingchao Zhang, Ian Chambers, Antonio Simeone
Embryonic stem cells (ESCs) cultured in leukemia inhibitory factor (LIF) plus fetal bovine serum (FBS) exhibit heterogeneity in the expression of naive and primed transcription factors. This heterogeneity reflects the dynamic condition of ESCs and their versatility to promptly respond to signaling effectors promoting naive or primed pluripotency. Here, we report that ESCs lacking Nanog or overexpressing Otx2 exhibit an early primed identity in LIF + FBS and fail to convert into 2i-induced naive state. Conversely, Otx2-null ESCs possess naive identity features in LIF + FBS similar to Nanog-overexpressing ESCs and convert poorly into FGF-induced early primed state...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29038581/transcriptional-repression-of-plxnc1-by-lmx1a-and-lmx1b-directs-topographic-dopaminergic-circuit-formation
#20
Audrey Chabrat, Guillaume Brisson, Hélène Doucet-Beaupré, Charleen Salesse, Marcos Schaan Profes, Axelle Dovonou, Cléophace Akitegetse, Julien Charest, Suzanne Lemstra, Daniel Côté, R Jeroen Pasterkamp, Monica I Abrudan, Emmanouil Metzakopian, Siew-Lan Ang, Martin Lévesque
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation...
October 16, 2017: Nature Communications
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