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https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#1
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27880803/wdr68-mediates-dorsal-and-ventral-patterning-events-for-craniofacial-development
#2
Estibaliz Alvarado, Mina Yousefelahiyeh, Greg Alvarado, Robin Shang, Taryn Whitman, Andrew Martinez, Yang Yu, Annie Pham, Anish Bhandari, Bingyan Wang, Robert M Nissen
Birth defects are among the leading causes of infant mortality and contribute substantially to illness and long-term disability. Defects in Bone Morphogenetic Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial syndromes are caused by defects in signaling pathways that pattern the cranial neural crest cells (CNCCs) along the dorsal-ventral axis. For example, auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling, and Alagille syndrome is caused by defects in Jagged-Notch signaling...
2016: PloS One
https://www.readbyqxmd.com/read/27835901/mutational-activation-of-braf-confers-sensitivity-to-transforming-growth-factor-beta-inhibitors-in-human-cancer-cells
#3
Lindsay C Spender, G John Ferguson, Sijia Liu, Chao Cui, Maria Romina Girotti, Gary Sibbet, Ellen B Higgs, Morven K Shuttleworth, Tom Hamilton, Paul Lorigan, Michael Weller, David F Vincent, Owen J Sansom, Margaret Frame, Peter Ten Dijke, Richard Marais, Gareth J Inman
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#4
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27795824/loss-of-mgat5a-mediated-n-glycosylation-stimulates-regeneration-in-zebrafish
#5
Wuhong Pei, Sunny C Huang, Lisha Xu, Kade Pettie, María Laura Ceci, Mario Sánchez, Miguel L Allende, Shawn M Burgess
BACKGROUND: We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified mgat5a, a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration. METHODS: We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish. We used pharmacological inhibition of N-glycosylation by swansonine...
2016: Cell Regeneration
https://www.readbyqxmd.com/read/27734462/microrna-200a-inhibits-erythroid-differentiation-by-targeting-pdcd4-and-thrb
#6
Yanming Li, Qian Zhang, Zhenglin Du, ZhiChao Lu, Shuge Liu, Lu Zhang, Nan Ding, Binghao Bao, Yadong Yang, Qian Xiong, Hai Wang, Zhaojun Zhang, Hongzhu Qu, Haibo Jia, Xiangdong Fang
Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid-inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF-1 cells confirmed its inhibitory role in erythroid differentiation...
October 13, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27649856/uncontrolled-sfk-mediated-protein-trafficking-in-prion-and-alzheimer-s-disease
#7
Edward Málaga-Trillo, Katharina Ochs
Prions and Amyloid beta (Aβ) peptides induce synaptic damage via complex mechanisms that include the pathological alteration of intracellular signaling cascades. The host-encoded cellular prion protein (PrP(C)) acts as a high-affinity cell surface receptor for both toxic species and it can modulate the endocytic trafficking of the N-methyl D-aspartate (NMDA) receptor and E-cadherin adhesive complexes via Src family kinases (SFKs). Interestingly, SFK-mediated control of endocytosis is a widespread mechanism used to regulate the activity of important transmembrane proteins, including neuroreceptors for major excitatory and inhibitory neurotransmitters...
September 2, 2016: Prion
https://www.readbyqxmd.com/read/27477184/smad4-is-required-for-the-development-of-cardiac-and-skeletal-muscle-in-zebrafish
#8
Jie Yang, Junnai Wang, Zhen Zeng, Long Qiao, Liang Zhuang, Lijun Jiang, Juncheng Wei, Quanfu Ma, Mingfu Wu, Shuangmei Ye, Qinglei Gao, Ding Ma, Xiaoyuan Huang
Transforming growth factor-beta (TGF-beta) regulates cellular functions and plays key roles in development and carcinogenesis. Smad4 is the central intracellular mediator of TGF-beta signaling and plays crucial roles in tissue regeneration, cell differentiation, embryonic development, regulation of the immune system and tumor progression. To clarify the role of smad4 in development, we examined both the pattern of smad4 expression in zebrafish embryos and the effect of smad4 suppression on embryonic development using smad4-specific antisense morpholino-oligonucleotides...
July 28, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27418134/microrna-184-promotes-differentiation-of-the-retinal-pigment-epithelium-by-targeting-the-akt2-mtor-signaling-pathway
#9
Chao Jiang, Bing Qin, Guohua Liu, Xiantao Sun, Houxia Shi, Sijia Ding, Yuan Liu, Meidong Zhu, Xue Chen, Chen Zhao
Dedifferentiation of retinal pigment epithelium (RPE) cells is a crucial contributing factor to the pathology of retinal degenerative diseases, including age-related macular degeneration (AMD). Herein, we aim to reveal the roles of microRNAs (miRNAs) in RPE dedifferentiation and seek for potential therapeutic targets. Based on the microarray data, miR-184 was sorted out as the most up-regulated signature along with the differentiation from human induced pluripotent stem cells (hiPSC) to RPE cells, suggesting its potential promotive role in RPE differentiation...
July 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27312501/zebrafish-pancreas-as-a-model-for-development-and-disease
#10
R A Kimmel, D Meyer
The vertebrate pancreas is composed of acinar tissue that produces digestive enzymes, a ductal system for transporting those enzymes, and the endocrine islets which produce hormones critical for organism glucose homeostasis. Recent studies have highlighted similarities between zebrafish and mammals in organ development, and increasingly reveal that the regulation of metabolic homeostasis is highly conserved as well. Use of zebrafish as a model organism, with its ease of genetic manipulation, high fecundity, and ready access for imaging, has been highly productive for studies of islet cell development...
2016: Methods in Cell Biology
https://www.readbyqxmd.com/read/27263412/visualizing-retinoic-acid-morphogen-gradients
#11
T F Schilling, J Sosnik, Q Nie
Morphogens were originally defined as secreted signaling molecules that diffuse from local sources to form concentration gradients, which specify multiple cell fates. More recently morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction. Many critical cell-cell signals implicated in both embryonic development and disease, such as Wnt, fibroblast growth factor (Fgf), hedgehog (Hh), transforming growth factor beta (TGFb), and retinoic acid (RA), are thought to act as morphogens, but key information on signal propagation and ligand distribution has been lacking for most...
2016: Methods in Cell Biology
https://www.readbyqxmd.com/read/27240166/tumor-suppression-in-basal-keratinocytes-via-dual-non-cell-autonomous-functions-of-a-na-k-atpase-beta-subunit
#12
Julia Hatzold, Filippo Beleggia, Hannah Herzig, Janine Altmüller, Peter Nürnberg, Wilhelm Bloch, Bernd Wollnik, Matthias Hammerschmidt
The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress)...
2016: ELife
https://www.readbyqxmd.com/read/27177910/the-pacific-white-shrimp-%C3%AE-actin-promoter-functional-properties-and-the-potential-application-for-transduction-system-using-recombinant-baculovirus
#13
Yingli Shi, Jianhai Xiang, Guangzhou Zhou, Tetsuzan Benny Ron, Hsin-I Tong, Wen Kang, Si Sun, Yuanan Lu
A newly isolated Pacific white shrimp (Litopenaeus vannamei) beta-actin promoter SbaP and its derivative compact construct SbaP (ENX) have recently been demonstrated to promote ectopic gene expression in vitro and in vivo. To further explore the potential transduction application, this newly isolated shrimp promoter SbaP was comparatively tested with cytomegalovirus (CMV), simian virus 40 (SV40), polyhedrin (Polh), and white spot syndrome virus immediate early gene 1 (WSSV ie1) four constitutive promoters and a beta-actin promoter (TbaP) from tilapia fish to characterize its promoting function in eight different cell lines...
June 2016: Marine Biotechnology
https://www.readbyqxmd.com/read/27166257/minimal-contribution-of-erk1-2-mapk-signalling-towards-the-maintenance-of-oncogenic-gnaqq209p-driven-uveal-melanomas-in-zebrafish
#14
Mai Abdel Mouti, Christopher Dee, Sarah E Coupland, Adam F L Hurlstone
Mutations affecting Gαq proteins are pervasive in uveal melanoma (UM), suggesting they 'drive' UM pathogenesis. The ERK1/2-MAPK pathway is critical for cutaneous melanoma development and consequently an important therapeutic target. Defining the contribution of ERK1/2-MAPK signalling to UM development has been hampered by the lack of an informative animal model that spontaneously develops UM. Towards this end, we engineered transgenic zebrafish to express oncogenic GNAQQ209P in the melanocyte lineage. This resulted in hyperplasia of uveal melanocytes, but with no evidence of malignant progression, nor perturbation of skin melanocytes...
June 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27065799/transcriptomic-analysis-of-purified-embryonic-neural-stem-cells-from-zebrafish-embryos-reveals-signaling-pathways-involved-in-glycine-dependent-neurogenesis
#15
Eric Samarut, Abdelhamid Bekri, Pierre Drapeau
How is the initial set of neurons correctly established during the development of the vertebrate central nervous system? In the embryo, glycine and GABA are depolarizing due the immature chloride gradient, which is only reversed to become hyperpolarizing later in post-natal development. We previously showed that glycine regulates neurogenesis via paracrine signaling that promotes calcium transients in neural stem cells (NSCs) and their differentiation into interneurons within the spinal cord of the zebrafish embryo...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/26938059/beta-catenin-and-plakoglobin-expression-during-zebrafish-tooth-development-and-replacement
#16
Barbara Verstraeten, Jolanda van Hengel, Ann Huysseune
We analyzed the protein distribution of two cadherin-associated molecules, plakoglobin and β-catenin, during the different stages of tooth development and tooth replacement in zebrafish. Plakoglobin was detected at the plasma membrane already at the onset of tooth development in the epithelial cells of the tooth. This pattern remained unaltered during further tooth development. The mesenchymal cells only showed plakoglobin from cytodifferentiation onwards. Plakoglobin 1a morpholino-injected embryos showed normal tooth development with proper initiation and differentiation...
2016: PloS One
https://www.readbyqxmd.com/read/26852117/multiple-signaling-factors-and-drugs-alleviate-neuronal-death-induced-by-expression-of-human-and-zebrafish-tau-proteins-in-vivo
#17
Bo-Kai Wu, Rey-Yue Yuan, Huang-Wei Lien, Chin-Chun Hung, Pung-Pung Hwang, Rita Pei-Yeh Chen, Chun-Che Chang, Yung-Feng Liao, Chang-Jen Huang
BACKGROUND: The axonal tau protein is a tubulin-binding protein, which plays important roles in the formation and stability of the microtubule. Mutations in the tau gene are associated with familial forms of frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17). Paired helical filaments of tau and extracellular plaques containing beta-amyloid are found in the brain of Alzheimer's disease (AD) patients. RESULTS: Transgenic models, including those of zebrafish, have been employed to elucidate the mechanisms by which tau protein causes neurodegeneration...
2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/26658317/an-insulin-signaling-feedback-loop-regulates-pancreas-progenitor-cell-differentiation-during-islet-development-and-regeneration
#18
Lihua Ye, Morgan A Robertson, Teresa L Mastracci, Ryan M Anderson
As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation...
January 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/26608985/thalidomide-effects-in-patients-with-hereditary-hemorrhagic-telangiectasia-during-therapeutic-treatment-and-in-fli-egfp-transgenic-zebrafish-model
#19
Hong-Ling Peng, Yi-Fang Yi, Shun-Ke Zhou, Si-Si Xie, Guang-Sen Zhang
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model. METHODS: HHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d)...
November 20, 2015: Chinese Medical Journal
https://www.readbyqxmd.com/read/26384018/diabetic-pdx1-mutant-zebrafish-show-conserved-responses-to-nutrient-overload-and-anti-glycemic-treatment
#20
Robin A Kimmel, Stefan Dobler, Nicole Schmitner, Tanja Walsen, Julia Freudenblum, Dirk Meyer
Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload...
2015: Scientific Reports
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