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Zebrafish pancreas

Sarah E Brown, Karilyn E Sant, Shana M Fleischman, Olivia Venezia, Monika A Roy, Ling Zhao, Alicia R Timme-Laragy
BACKGROUND: Butylparaben (butyl p-hydroxybenzoic acid) is a common cosmetic and pharmaceutical preservative reported to induce oxidative stress and endocrine disruption. Embryonic development is sensitive to oxidative stress, with redox potentials playing critical roles in progenitor cell fate decisions. Because pancreatic beta cells have been reported to have low antioxidant gene expression, they may be sensitive targets of oxidative stress. We tested the hypotheses that butylparaben causes oxidative stress in the developing embryo, and that pancreatic beta cells are a sensitive target of butylparaben embryotoxicity...
March 8, 2018: Birth Defects Research
Julia Freudenblum, José A Iglesias, Martin Hermann, Tanja Walsen, Armin Wilfinger, Dirk Meyer, Robin A Kimmel
The three-dimensional architecture of the pancreatic islet is critical for beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time lapse and longitudinal imaging studies to follow islet develoment, visualizing both naturally occuring islet cells and cells arising with an accelerated time course following an induction approach...
January 31, 2018: Development
Massimo Venditti, Aldo Donizetti, Marcella Fiengo, Chiara Fasano, Alessandra Santillo, Francesco Aniello, Sergio Minucci
Relaxin (RLN) and insulin (INSL)-like peptides are member of the INSL/RLN superfamily, which are encoded by seven genes in humans and can activate the G-protein coupled receptor RXFP 1-4. These peptides evolved from a common ancestor, RLN3-like gene. Two rounds of whole genome duplication (WGD) in early vertebrate evolution, together with an additional WGD in the teleost lineage, caused an expansion of RLN genes set in the genome of Danio rerio. In particular, six RLN genes are present: a single copy of rln and insl3 genes, and two paralogs for the rln3 gene (rln3a and rln3b), and the insl5 gene (insl5a and insl5b)...
January 10, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Haydee M Jacobs, Karilyn E Sant, Aviraj Basnet, Larissa M Williams, Jennifer B Moss, Alicia R Timme-Laragy
Mono(2-ethylhexyl) phthalate (MEHP) is the bioactive metabolite of di(2-ethylhexyl) phthalate, a plasticizing agent and persistent environmental contaminant associated with obesity, developmental abnormalities, and oxidative stress. Nrf2 (Nfe2l2) is a transcription factor that regulates cytoprotective genes as part of the adaptive antioxidant response. We previously identified the pancreas as a sensitive target of oxidative stress during embryonic development. The goals of this study were to 1) characterize the effects of MEHP exposure on pancreatic development, and 2) determine whether oxidative stress contributes to MEHP embryotoxicity...
December 15, 2017: Chemosphere
Ting-Shuan Wu, Yu-Ting Lin, Ying-Tzu Huang, Ya-Chih Cheng, Feng-Yih Yu, Biing-Hui Liu
Ochratoxin A (OTA) is a mycotoxin that is found in various food and feed products. The molecular mechanisms that are associated with OTA hepatotoxicity and teratogenicity have not been extensively elucidated in a developing organism. In this study, the transcriptomic profile of zebrafish embryos indicates that hemostasis and blood coagulation are the top two pathways affected by OTA. The treatment of embryos with OTA was able to decrease the expression of genes that encode coagulation factors and liver markers, including f7, f9b, cp and vtna...
December 21, 2017: Toxicology and Applied Pharmacology
Georgia Wyett, Yann Gibert, Megan Ellis, Hozana A Castillo, Jan Kaslin, Kathryn Aston-Mourney
PURPOSE: Type 1 and 2 diabetes are characterized by a loss of insulin-producing beta-cells. Current treatments help maintain blood glucose levels but cannot provide a cure. As such, a vital target for the cure of diabetes is a way to restore beta-cell mass. The drug metformin can protect cultured beta-cells/islets from hyperglycemia-induced dysfunction and death. Further, treatment of pregnant mice with metformin results in an enhanced beta-cell fraction in the embryos; however, whether this occurs via a direct effect is unknown...
December 22, 2017: Endocrine
Jia He, Yun Yang, Junren Zhang, Jinzi Chen, Xiangyong Wei, Jianbo He, Lingfei Luo
Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs...
December 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Vanessa H Quinlivan, Steven A Farber
The developing zebrafish is a well-established model system for studies of energy metabolism, and is amenable to genetic, physiological, and biochemical approaches. For the first 5 days of life, nutrients are absorbed from its endogenous maternally deposited yolk. At 5 days post-fertilization, the yolk is exhausted and the larva has a functional digestive system including intestine, liver, gallbladder, pancreas, and intestinal microbiota. The transparency of the larval zebrafish, and the genetic and physiological similarity of its digestive system to that of mammals make it a promising system in which to address questions of energy homeostasis relevant to human health...
2017: Frontiers in Endocrinology
Michiel van Veen, Laurie A Mans, Elisa Matas-Rico, Jason van Pelt, Anastassis Perrakis, Wouter H Moolenaar, Anna-Pavlina G Haramis
Notch signaling plays an essential role in the proliferation, differentiation and cell fate determination of various tissues, including the developing pancreas. One regulator of the Notch pathway is GDE2 (or GDPD5), a transmembrane ecto-phosphodiesterase that cleaves GPI-anchored proteins at the plasma membrane, including a Notch ligand regulator. Here we report that Gdpd5-knockdown in zebrafish embryos leads to developmental defects, particularly, impaired motility and reduced pancreas differentiation, as shown by decreased expression of insulin and other pancreatic markers...
January 2018: International Journal of Biochemistry & Cell Biology
Jordan A Pitt, Jordan S Kozal, Nishad Jayasundara, Andrey Massarsky, Rafael Trevisan, Nick Geitner, Mark Wiesner, Edward D Levin, Richard T Di Giulio
Plastic pollution is a critical environmental concern and comprises the majority of anthropogenic debris in the ocean, including macro, micro, and likely nanoscale (less than 100nm in at least one dimension) plastic particles. While the toxicity of macroplastics and microplastics is relatively well studied, the toxicity of nanoplastics is largely uncharacterized. Here, fluorescent polystyrene nanoparticles (PS NPs) were used to investigate the potential toxicity of nanoplastics in developing zebrafish (Danio rerio), as well as to characterize the uptake and distribution of the particles within embryos and larvae...
January 2018: Aquatic Toxicology
Danhua Zhang, Keith P Gates, Lindsey Barske, Guangliang Wang, Joseph J Lancman, Xin-Xin I Zeng, Megan Groff, Kasper Wang, Michael J Parsons, J Gage Crump, P Duc Si Dong
Liver duct paucity is characteristic of children born with Alagille Syndrome (ALGS), a disease associated with JAGGED1 mutations. Here, we report that zebrafish embryos with compound homozygous mutations in two Notch ligand genes, jagged1b (jag1b) and jagged2b (jag2b) exhibit a complete loss of canonical Notch activity and duct cells within the liver and exocrine pancreas, whereas hepatocyte and acinar pancreas development is not affected. Further, animal chimera studies demonstrate that wild-type endoderm cells within the liver and pancreas can rescue Notch activity and duct lineage specification in adjacent cells lacking jag1b and jag2b expression...
October 3, 2017: Nature Communications
Raphael Carapito, Martina Konantz, Catherine Paillard, Zhichao Miao, Angélique Pichot, Magalie S Leduc, Yaping Yang, Katie L Bergstrom, Donald H Mahoney, Deborah L Shardy, Ghada Alsaleh, Lydie Naegely, Aline Kolmer, Nicodème Paul, Antoine Hanauer, Véronique Rolli, Joëlle S Müller, Elisa Alghisi, Loïc Sauteur, Cécile Macquin, Aurore Morlon, Consuelo Sebastia Sancho, Patrizia Amati-Bonneau, Vincent Procaccio, Anne-Laure Mosca-Boidron, Nathalie Marle, Naël Osmani, Olivier Lefebvre, Jacky G Goetz, Sule Unal, Nurten A Akarsu, Mirjana Radosavljevic, Marie-Pierre Chenard, Fanny Rialland, Audrey Grain, Marie-Christine Béné, Marion Eveillard, Marie Vincent, Julien Guy, Laurence Faivre, Christel Thauvin-Robinet, Julien Thevenon, Kasiani Myers, Mark D Fleming, Akiko Shimamura, Elodie Bottollier-Lemallaz, Eric Westhof, Claudia Lengerke, Bertrand Isidor, Seiamak Bahram
Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa)...
November 1, 2017: Journal of Clinical Investigation
Margrit Kamel, Nikolay Ninov
Traditionally, the development of novel therapeutics for metabolic diseases has relied mainly on high-throughput screening using biochemical or cell-based assays. While this approach represents a driving force in drug discovery, there is also a need to perform large-scale screens without disrupting inter-organ communication and tissue architecture, essential components for understanding the complexity of metabolic regulation and the identification of small molecules with appropriate biological activities in vivo...
December 2017: Current Opinion in Pharmacology
Nicola Facchinello, Estefania Tarifeño-Saldivia, Enrico Grisan, Marco Schiavone, Margherita Peron, Alessandro Mongera, Olivier Ek, Nicole Schmitner, Dirk Meyer, Bernard Peers, Natascia Tiso, Francesco Argenton
Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration...
August 29, 2017: Scientific Reports
Liqing Zang, Yasuhito Shimada, Norihiro Nishimura
Obesity is a major cause of type 2 diabetes mellitus (T2DM) in mammals. We have previously established a zebrafish model of diet-induced obesity (DIO zebrafish) by overfeeding Artemia. Here we created DIO zebrafish using a different method to induce T2DM. Zebrafish were overfed a commercially available fish food using an automated feeding system. We monitored the fasting blood glucose levels in the normal-fed group (one feed/day) and overfed group (six feeds/day) over an 8-week period. The fasting blood glucose level was significantly increased in DIO zebrafish compared with that of normal-fed zebrafish...
May 3, 2017: Scientific Reports
So Jung Kwon, Su Jung Hwang, Yeonghun Jung, Hyeung-Geun Park, Mi-Hyun Kim, Yohan Park, Hyo-Jong Lee
OBJECTIVE: The extracts of Nitraria genus are composed of Nitraria alkaloids and have been used traditionally as a hypoglycemic medicine. However, the efficacy and precise mechanism of Nitraria alkaloids remain largely unknown. METHODS: Previously, we reported the total synthesis of (+)-isonitramine, one of Nitraria alkaloids. In this study, we investigated the anti-diabetic potential of isonitramine in diabetes mellitus and its underlying molecular mechanism in carbohydrate catabolism in vitro and in vivo...
May 2017: Metabolism: Clinical and Experimental
Karilyn E Sant, Haydee M Jacobs, Jiali Xu, Katrina A Borofski, Larry G Moss, Jennifer B Moss, Alicia R Timme-Laragy
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio)...
September 2016: Toxics
Christopher H Emfinger, Alecia Welscher, Zihan Yan, Yixi Wang, Hannah Conway, Jennifer B Moss, Larry G Moss, Maria S Remedi, Colin G Nichols
ATP-sensitive potassium channels (KATP channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATP channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts...
February 2017: Royal Society Open Science
Rebekah M Charney, Kitt D Paraiso, Ira L Blitz, Ken W Y Cho
Germ layer formation is among the earliest differentiation events in metazoan embryos. In triploblasts, three germ layers are formed, among which the endoderm gives rise to the epithelial lining of the gut tube and associated organs including the liver, pancreas and lungs. In frogs (Xenopus), where early germ layer formation has been studied extensively, the process of endoderm specification involves the interplay of dozens of transcription factors. Here, we review the interactions between these factors, summarized in a transcriptional gene regulatory network (GRN)...
June 2017: Seminars in Cell & Developmental Biology
Victoria E Prince, Ryan M Anderson, Gokhan Dalgin
The zebrafish pancreas shares its basic organization and cell types with the mammalian pancreas. In addition, the developmental pathways that lead to the establishment of the pancreatic islets of Langherhans are generally conserved from fish to mammals. Zebrafish provides a powerful tool to probe the mechanisms controlling establishment of the pancreatic endocrine cell types from early embryonic progenitor cells, as well as the regeneration of endocrine cells after damage. This knowledge is, in turn, applicable to refining protocols to generate renewable sources of human pancreatic islet cells that are critical for regulation of blood sugar levels...
2017: Current Topics in Developmental Biology
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