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Zebrafish pancreas

Wei Huang, Rebecca L Beer, Fabien Delaspre, Guangliang Wang, Hannah E Edelman, Hyewon Park, Mizuki Azuma, Michael J Parsons
Centroacinar cells (CACs) are ductal Notch-responsive progenitors that in the larval zebrafish pancreas differentiate to form new islets and ultimately contribute to the majority of the adult endocrine mass. Uncovering the mechanisms regulating CAC differentiation will facilitate understanding how insulin-producing β cells are formed. Previously we reported retinoic acid (RA) signaling and Notch signaling both regulate larval CAC differentiation, suggesting a shared downstream intermediate. Sox9b is a transcription factor important for islet formation whose expression is upregulated by Notch signaling in larval CACs...
October 1, 2016: Developmental Biology
L Pu, L C Zhang, J S Zhang, X Song, L G Wang, J Liang, Y B Zhang, X Liu, H Yan, T Zhang, J W Yue, N Li, Q Q Wu, L X Wang
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is essential for apoptosis, proliferation, differentiation, and immune responses, and is a candidate marker for residual feed intake (RFI) in pig. We cloned the full-length cDNA sequence of porcine MAP3K5 by rapid-amplification of cDNA ends. The 5451-bp gene contains a 5'-untranslated region (UTR) (718 bp), a coding region (3738 bp), and a 3'-UTR (995 bp), and encodes a peptide of 1245 amino acids, which shares 97, 99, 97, 93, 91, and 84% sequence identity with cattle, sheep, human, mouse, chicken, and zebrafish MAP3K5, respectively...
2016: Genetics and Molecular Research: GMR
Adriana López-Barradas, Tania González-Cid, Norma Vazquez, Marisol Gavi-Maza, Adriana Reyes-Camacho, Laura Alejandra Velazquez-Villegas, Victoria Ramirez, Kambiz Zandi-Nejad, David B Mount, Nimbe Torres, Armando R Tovar, Michael F Romero, Gerardo Gamba, Consuelo Plata
SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent (22)Na(+) uptake by 29%. Consistent with this result, the co-injection of SMCT1 with SGK1 cRNA decreased the KIC-dependent (22)Na(+) uptake by 34%...
August 3, 2016: American Journal of Physiology. Cell Physiology
Sahar Nissim, Olivia Weeks, Jared C Talbot, John W Hedgepeth, Julia Wucherpfennig, Stephanie Schatzman-Bone, Ian Swinburne, Mauricio Cortes, Kristen Alexa, Sean Megason, Trista E North, Sharon L Amacher, Wolfram Goessling
The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development...
October 1, 2016: Developmental Biology
W Goessling, D Y Stainier
The endoderm is the innermost embryonic germ layer, and in zebrafish, it gives rise to the lining of the gut, the gills, liver, pancreas, gallbladder, and derivatives of the pharyngeal pouch. These organs form the gastrointestinal tract and are involved with the absorption, delivery, and metabolism of nutrients. The liver has a central role in regulating these processes because it controls carbohydrate and lipid metabolism, protein synthesis, and breakdown of endogenous and xenobiotic products. Liver dysfunction frequently leads to significant morbidity and mortality; however, in most settings of organ injury, the liver exhibits remarkable regenerative capacity...
2016: Methods in Cell Biology
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
Y Cui, S Lv, J Liu, S Nie, J Chen, Q Dong, C Huang, D Yang
Perfluorooctanesulfonic acid (PFOS), a ubiquitous contaminant, has been used in various industrial applications. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism in F0 adult zebrafish and F1 offspring. Our findings revealed a severe fatty degeneration in the liver of F0 males treated with 0.5 μM PFOS and significant ultrastructure changes associated with substance transport or metabolism in liver and intestines (abnormal mitochondria and endoplasmic reticulum, disordered arrangement of inner microvilli within intracellular canaliculus)...
May 18, 2016: Human & Experimental Toxicology
Bilge San, Naomi D Chrispijn, Nadine Wittkopp, Simon J van Heeringen, Anne K Lagendijk, Marco Aben, Jeroen Bakkers, René F Ketting, Leonie M Kamminga
Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many of which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer of zeste homolog 2 (Ezh2), the PcG protein responsible for placing the transcriptional repressive H3K27me3 mark. We identified a nonsense mutant of ezh2 and generated maternal zygotic (MZ) ezh2 mutant embryos. In contrast to knockout mice for PcG proteins, MZezh2 mutant embryos gastrulate seemingly normal, but die around 2 days post fertilization displaying pleiotropic phenotypes...
2016: Scientific Reports
Man Wang, Lingyi Li, Quanyang Guo, Shicui Zhang, Dongrui Ji, Hongyan Li
Lymphocyte antigen-6 (Ly6) superfamily is a large family of proteins and characterized by precisely spaced cysteine motifs, termed the three-finger fold. To date, a large number of members of the Ly6/uPAR family were identified among many species. In this study, we first report the identification and characterization of the secreted Ly2.1-3 proteins on the chromosome 2 in zebrafish and determine the expression pattern. Ly2.1-3 all possess a conserved LU domain and adopt similar three-finger structure with human CD59, SLURP1 and other Ly6 family members...
July 2016: Fish & Shellfish Immunology
Rebecca L Beer, Michael J Parsons, Meritxell Rovira
The process of regeneration serves to heal injury by replacing missing cells. Understanding regeneration can help us replace cell populations lost during disease, such as the insulin-producing β cells lost in diabetic patients. Centroacinar cells (CACs) are a specialized ductal pancreatic cell type that act as progenitors to replace β cells in the zebrafish. However, whether CACs contribute to β-cell regeneration in adult mammals remains controversial. Here we review the current understanding of the role of CACs as endocrine progenitors during regeneration in zebrafish and mammals...
May 1, 2016: Developmental Biology
Tom Stiff, Teresa Casar Tena, Mark O'Driscoll, Penny A Jeggo, Melanie Philipp
Mutations in ATR(ataxia telangiectasia and RAD3-related) cause Seckel syndrome (ATR-SS), a microcephalic primordial dwarfism disorder. Hitherto, the clinical manifestation of ATR deficiency has been attributed to its canonical role in DNA damage response signalling following replication fork stalling/collapse. Here, we show that ATR regulates cilia-dependent signalling in a manner that can be uncoupled from its function during replication. ATR-depleted or patient-derived ATR-SS cells form cilia of slightly reduced length but are dramatically impaired in cilia-dependent signalling functions, including growth factor and Sonic hedgehog signalling...
April 15, 2016: Human Molecular Genetics
Ling Li, François Bonneton, Marie Tohme, Laure Bernard, Xiao Yong Chen, Vincent Laudet
The effects of endocrine disrupting chemicals (EDCs) on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio) transgenic lines expressing the green fluorescent protein (GFP) in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish...
2016: PloS One
Jin Xu, Jiaxi Cui, Aranzazu Del Campo, Chong Hyun Shin
The liver and pancreas originate from overlapping embryonic regions, and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b) signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b), which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling...
February 2016: PLoS Genetics
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
Ewa Bielczyk-Maczyńska, Laure Lam Hung, Lauren Ferreira, Tobias Fleischmann, Félix Weis, Antonio Fernández-Pevida, Steven A Harvey, Neha Wali, Alan J Warren, Inês Barroso, Derek L Stemple, Ana Cvejic
Ribosome biogenesis is a ubiquitous and essential process in cells. Defects in ribosome biogenesis and function result in a group of human disorders, collectively known as ribosomopathies. In this study, we describe a zebrafish mutant with a loss-of-function mutation in nol9, a gene that encodes a non-ribosomal protein involved in rRNA processing. nol9sa1022/sa1022 mutants have a defect in 28S rRNA processing. The nol9sa1022/sa1022 larvae display hypoplastic pancreas, liver and intestine and have decreased numbers of hematopoietic stem and progenitor cells (HSPCs), as well as definitive erythrocytes and lymphocytes...
December 2015: PLoS Genetics
Gideon Hen, Julian Nicenboim, Oded Mayseless, Lihee Asaf, Masahiro Shin, Giorgia Busolin, Roy Hofi, Gabriella Almog, Natascia Tiso, Nathan D Lawson, Karina Yaniv
Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. Although it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels and the molecular mechanisms regulating their formation are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas and, as such, represents an ideal model in which to investigate the early steps of organ-specific vessel formation...
December 15, 2015: Development
Maria Cristina Guerrera, Francesca De Pasquale, Ugo Muglia, Gabriella Caruso
Despite the growing importance of zebrafish (Danio rerio) as an experimental model in biomedical research, some aspect of physiological and related morphological age dependent changes in digestive system during larval development are still unknown. In this paper, a biochemical and morphological study of the digestive tract of zebrafish was undertaken to record the functional changes occurring in this species during its ontogenetic development, particularly from 24 hr to 47 days post fertilization (dpf). Endo- and exo-proteases, as well as α-amylase enzymes, were quantified in zebrafish larvae before first feeding (7 dpf)...
December 2015: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Teresa L Mastracci, Morgan A Robertson, Raghavendra G Mirmira, Ryan M Anderson
The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis...
2015: Scientific Reports
Guangliang Wang, Surendra K Rajpurohit, Fabien Delaspre, Steven L Walker, David T White, Alexis Ceasrine, Rejji Kuruvilla, Ruo-Jing Li, Joong S Shim, Jun O Liu, Michael J Parsons, Jeff S Mumm
Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific fluorescent reporters in >500,000 transgenic zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs that increased the number of insulin-producing β cells in the pancreas...
2015: ELife
Fabien Delaspre, Rebecca L Beer, Meritxell Rovira, Wei Huang, Guangliang Wang, Stephen Gee, Maria del Carmen Vitery, Sarah J Wheelan, Michael J Parsons
Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors...
October 2015: Diabetes
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