Her6 Regulates the Neurogenetic Gradient and Neuronal Identity in the Thalamus
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Fish Mutant, Where Is Thy Phenotype?
PERSPECTIVE Fish mutant, where is thy phenotype? Darius Balciunas* Department of Biology, Temple University, Philadelphia, Pennsylvania, United States of America * [email protected] The field of genetics emerged as a study of the inheritance of desirable or otherwise interesting traits. Mutations were characterized as recessive or dominant, assigned to complementation groups, mapped, and finally, the affected genes were identified. By default, recessive mutations could only be isolated in genes that played an important role in the biological process of inter- est, be it pea color or segmentation pattern of the fruit fly embryo. As methodologies to mutate specific genes in various model systems were developed, scien- tists began to employ reverse genetics, whereby a gene of interest is selected and a mutant is generated. Ideally, the mutant displays a phenotype that can be studied (green panels in Fig 1). Such best-case scenarios pose the danger of confirmation bias ([1] and references therein). It may therefore be prudent to validate the phenotype by engineering an independent mutant allele. This is especially straightforward in zebrafish, given that targeted mutagenesis using CRISPR/Cas9 requires relatively little effort [2±4]. In zebrafish, the phenotype may also be confirmed by performing knockdown using morpholino oligonucleotides [5±6]. a1111111111 Real experiments rarely follow best-case scenarios, and very frequently, mutants generated a1111111111 by reverse genetics fail to display overt phenotypes. Are the majority of protein-coding genes a1111111111 indeed not required, often despite a very high degree of evolutionary conservation? Genetic a1111111111 redundancy, most obviously in the form of homologous or duplicated genes, certainly contrib- a1111111111 utes to a lack of mutant phenotypes. -
Deficits in Early Neural Tube Identity Found in CHARGE Syndrome
INSIGHT elife.elifesciences.org CEREBELLAR MALFORMATION Deficits in early neural tube identity found in CHARGE syndrome Long predicted from studies of model vertebrates, the first human example of abnormal patterning of the early neural tube leading to underdevelopment of the cerebellum has been demonstrated. PARTHIV HALDIPUR AND KATHLEEN J MILLEN work by Yu et al. shows that loss of CHD7 also Related research article Yu T, Meiners LC, disrupts the development of the early neural tube, Danielsen K, Wong MTY, Bowler T, which is the forerunner of the central nervous sys- Reinberg D, Scambler PJ, van Ravenswaaij- tem. This results in underdevelopment (hypoplasia) of the cerebellar vermis. This finding is extremely Arts CMA, Basson MA. 2013. Deregulated exciting as it represents the very first example of FGF and homeotic gene expression this particular class of neural birth defect to be underlies cerebellar vermis hypoplasia in observed in humans. CHARGE syndrome. eLife 2:e01305. One of the first steps in the development of the central nervous system is the establishment of doi: 10.7554/eLife.01305 gene expression domains that segment the neural Image MRI scan of a patient with CHARGE tube into the regions that become the forebrain, syndrome the midbrain, the hindbrain and the spinal cord. Subsequently, signalling centres establish the boundaries between these regions and secrete HARGE syndrome is a genetic condition growth factors which pattern the adjacent nervous that involves multiple malformations in tissue (Kiecker and Lumsden, 2012). The best Cnewly born children. The acronym stands understood signalling centre is the Isthmic for coloboma (a hole in the eye), heart defects, Organizer, which forms at the boundary of the choanal atresia (a blockage of the nasal pas- midbrain and the hindbrain. -
Table of Contents
Table of Contents 1. - EXAMINING ATTITUDES AND WILLINGNESS TO PAY FOR AQUACULTURED SEAFOOD ATTRIBUTES I. Ko Britwum * II. Caroline Noblet 2. - Development of a Hybrid Thermoplastic Composite and Concrete Deck System I. Benjamin Smith * II. William Davids 3. - Undergraduate Nursing Students’ Perspectives and Attitudes Caring for Elderly Patients at End of Life I. Karen Chase * II. Patricia Poirier 4. - Backpack Programs: How Maine Elementary Schools Are Tackling Childhood Hunger I. Julianna Acheson * II. Julia Van Steenberge III. Dean Rando IV. Ashlee Atchinson V. Sandra Caron 5. - Using Structure from Motion and 3D Printing as a Method for Preserving the Petroglyphs of Machias Bay, Maine I. Kendra Bird * II. Lisa Neuman 6. - Capacity Assessment of Older T-Beam Bridges Using Field Load Testing and Nonlinear Proxy Finite-Element Analysis I. Andrew Schanck * II. William Davids 7. - Interventions Supporting Social Communication Skills in Preschool-Aged Children with Autism Spectrum Disorder I. Paige Hanson * II. Paige Castonguay III. Heather Lowry IV. Taylor Dupont V. Paige Lane 8. - Attitudes Towards Immigration Following the 2018 Family Separation Crisis: Content Analysis of Tweets in The Washington Post vs Fox News I. Rebecca Blodgett * II. Vincent Eze III. Ariana Cruwys IV. Sandra Caron 9. - Nurses Role in Central Line-Associated Bloodstream Infection Prevention I. Laura Roberts * II. Julia Schnee III. Bronwyn West IV. Alex Roderick V. Valerie Herbert 10. - Overwintering strategies of the salmon louse Lepeophtheirus salmonis I. Emma Taccardi * II. Carrie Byron III. Ian Bricknell 11. - The eects of diverse aged enrollment on community school literacy rates in rural Zambia: Case study on Impact Network International schools, Eastern Province Zambia I. -
Induced Early Expression of Mrf4 but Not Myog Rescues Myogenesis in the Myod/Myf5 Double- Morphant Zebrafish Embryo
Research Article 481 Induced early expression of mrf4 but not myog rescues myogenesis in the myod/myf5 double- morphant zebrafish embryo Esther Schnapp1,*, Anna Silvia Pistocchi2,*, Evangelia Karampetsou2, Efrem Foglia2, Carla Lora Lamia2, Franco Cotelli2,‡ and Giulio Cossu1,2,‡ 1Stem Cell Research Institute, DiBiT, San Raffaele Scientific Institute, 58 via Olgettina, 20132 Milan, Italy 2Department of Biology, University of Milan, 26 via Celoria, 20133 Milan, Italy *These authors contributed equally to this work ‡Authors for correspondence (e-mails: [email protected]; [email protected]) Accepted 13 October 2008 Journal of Cell Science 122, 481-488 Published by The Company of Biologists 2009 doi:10.1242/jcs.038356 Summary Muscle regulatory factors activate myogenesis in all vertebrates, inhibition, we were able to investigate how myogenesis occurs in but their role has been studied in great detail only in the mouse the absence of a myotome. We report that in the complete absence embryo, where all but myogenin – Myod, Myf5 and Mrf4 – are of a myotome, subsequent myogenesis is abolished, whereas sufficient to activate (albeit not completely) skeletal myogenesis. myogenesis does proceed, albeit abnormally, when the In the zebrafish embryo, myod and myf5 are required for morpholino inhibition was not complete. Therefore our data also induction of myogenesis because their simultaneous ablation show that the early myotome is essential for subsequent skeletal prevents muscle development. Here we show that mrf4 but not muscle differentiation and patterning in the zebrafish. myog can fully rescue myogenesis in the myod/myf5 double morphant via a selective and robust activation of myod, in keeping Supplementary material available online at with its chromatin-remodelling function in vitro. -
Characterization of Ncf1 Mutants in a Zebrafish Model of Innate Immune Function with Human Influenza a Virus Infection
The University of Maine DigitalCommons@UMaine Honors College Spring 5-2020 Characterization of ncf1 Mutants in a Zebrafish Model of Innate Immune Function with Human Influenza A Virus Infection Lily Charpentier Follow this and additional works at: https://digitalcommons.library.umaine.edu/honors Part of the Immunology and Infectious Disease Commons, Influenza Humans Commons, and the Virus Diseases Commons This Honors Thesis is brought to you for free and open access by DigitalCommons@UMaine. It has been accepted for inclusion in Honors College by an authorized administrator of DigitalCommons@UMaine. For more information, please contact [email protected]. CHARACTERIZATION OF NCF1 MUTANTS IN A ZEBRAFISH MODEL OF INNATE IMMUNE FUNCTION WITH HUMAN INFLUENZA A VIRUS INFECTION by Lily Charpentier A Thesis Submitted to Partial Fulfillment of the Requirements for a Degree with Honors (Biochemistry) The Honors College The University of Maine May 2020 Advisory Committee: Benjamin L. King, Assistant Professor of Bioinformatics, Advisor Edward Bernard, Lecturer & Undergraduate Coordinator of Molecular & Biomedical Sciences R.W. Estela, Honors Preceptor Sally D. Molloy, Assistant Professor of Genomics Robert Wheeler, Associate Professor of Microbiology ABSTRACT Seasonal influenza A virus (IAV) infections and their associated respiratory diseases are the cause of an estimated 650,000 deaths each year, according to the World Health Organization. The zebrafish (Danio rerio) is a powerful vertebrate model to study innate immune function and host-pathogen interactions as the function of neutrophils and other phagocytes can be characterized in vivo. Preliminary studies have shown an increase in neutrophil respiratory burst activity to eliminate the invading pathogen, yet little is known of all of the mechanisms involved in neutrophil function. -
HHS Public Access Author Manuscript
HHS Public Access Author manuscript Author Manuscript Author ManuscriptNat Genet Author Manuscript. Author manuscript; Author Manuscript available in PMC 2015 November 01. Published in final edited form as: Nat Genet. 2015 May ; 47(5): 528–534. doi:10.1038/ng.3256. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction Naiara Akizu1,2,3, Vincent Cantagrel4, Maha S. Zaki5, Lihadh Al-Gazali6, Xin Wang1,2, Rasim Ozgur Rosti1,2, Esra Dikoglu1,2, Antoinette Bernabe Gelot7,8, Basak Rosti1,2, Keith K. Vaux1,2, Eric M. Scott1,2, Jennifer L. Silhavy1,2, Jana Schroth1,2, Brett Copeland1,2, Ashleigh E. Schaffer1,2, Philip Gordts9, Jeffrey D. Esko9, Matthew D. Buschman10, Seth J. Fields10, Gennaro Napolitano11, R. Koksal Ozgul12, Mahmut Samil Sagiroglu13, Matloob Azam14, Samira Ismail5, Mona Aglan5, Laila Selim15, Iman Gamal15, Sawsan Abdel Hadi15, Amera El Badawy15, Abdelrahim A. Sadek16, Faezeh Mojahedi17, Hulya Kayserili18, Amira Masri19, Laila Bastaki20, Samia Temtamy5, Ulrich Müller3, Isabelle Desguerre21, Jean- Laurent Casanova2,22,23, Ali Dursun24, Murat Gunel25,26,27, Stacey B. Gabriel28, Pascale de Lonlay29, and Joseph G. Gleeson1,2,30 1Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065. USA. 2Howard Hughes Medical Institute. Chevy Chase, Maryland, USA. 3Dorris Neuroscience Center, Scripps Research Institute, La Jolla, CA 92093, USA. 4Institut Imagine, INSERM U1163, Hôpital Necker Enfants Malades, PARIS, France 75743. 5Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, 12311 Egypt. 6College of Medicine and Health Sciences, UAE University, United Arab Emirates. 7AP-HP, Hôpital Armand Trousseau, Laboratoire d’Anatomie Pathologique, Neuropathologie, Paris, France. -
BMC Developmental Biology Biomed Central
CORE Metadata, citation and similar papers at core.ac.uk Provided by PubMed Central BMC Developmental Biology BioMed Central Research article Open Access laminin alpha 1 gene is essential for normal lens development in zebrafish Natalya S Zinkevich†1,2, Dmitry V Bosenko†1,2, Brian A Link2 and Elena V Semina*1,2,3 Address: 1Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA, 2Departments of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA and 3Departments of Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA Email: Natalya S Zinkevich - [email protected]; Dmitry V Bosenko - [email protected]; Brian A Link - [email protected]; Elena V Semina* - [email protected] * Corresponding author †Equal contributors Published: 07 March 2006 Received: 28 September 2005 Accepted: 07 March 2006 BMC Developmental Biology2006, 6:13 doi:10.1186/1471-213X-6-13 This article is available from: http://www.biomedcentral.com/1471-213X/6/13 © 2006Zinkevich et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Laminins represent major components of basement membranes and play various roles in embryonic and adult tissues. The functional laminin molecule consists of three chains, alpha, beta and gamma, encoded by separate genes. There are twelve different laminin genes identified in mammals to date that are highly homologous in their sequence but different in their tissue distribution. -
NIH Public Access Author Manuscript Nature
NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2013 November 08. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nature. 2009 January 8; 457(7226): . doi:10.1038/nature07520. The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear Jessica R. Colantonio1,*, Julien Vermot4,*, David Wu4, Adam D. Langenbacher2, Scott Fraser4, Jau-Nian Chen2,3, and Kent L. Hill1,3 1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA 2Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California 90095, USA 3Molecular Biology Institute, University of California, Los Angeles, California 90095, USA 4Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA Abstract In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin-based microvilli and microtubule-based cilia that extend from the surface of sensory hair cells and attach to biomineralized ‘ear stones’ (or otoliths)1. Otolith number, size and placement are under strict developmental control, but the mechanisms that ensure otolith assembly atop specific cells of the sensory epithelium are unclear. Here we demonstrate that cilia motility is required for normal otolith assembly and localization. Using in vivo video microscopy, we show that motile tether cilia at opposite poles of the otic vesicle create fluid vortices that attract otolith precursor particles, thereby biasing an otherwise random distribution to direct localized otolith seeding on tether cilia. Independent knockdown of subunits for the dynein regulatory complex and outer-arm dynein disrupt cilia motility, leading to defective otolith biogenesis. -
Wnt Signal Specifies the Intrathalamic Limit and Its Organizer Properties by Regulating Shh Induction in the Alar Plate
The Journal of Neuroscience, February 27, 2013 • 33(9):3967–3980 • 3967 Development/Plasticity/Repair Wnt Signal Specifies the Intrathalamic Limit and Its Organizer Properties by Regulating Shh Induction in the Alar Plate Almudena Martinez-Ferre,* Maria Navarro-Garberi,* Carlos Bueno, and Salvador Martinez Institute of Neurosciences, Miguel Herna´ndez University–Spanish National Research Council, 03550 San Juan, Alicante, Spain The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the alar plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center. Shh is expressed early on in the prosencephalic basal plate and is then gradually activated dorsally within the ZLI. The anteroposterior posi- tioning and the mechanism inducing Shh expression in ZLI cells are still partly unknown, being a subject of controversial interpretations. For instance, separate experimental results have suggested that juxtaposition of prechordal (rostral) and epichordal (caudal) neuroep- ithelium, anteroposterior encroachment of alar lunatic fringe (L-fng) expression, and/or basal Shh signaling is required for ZLI specifi- cation. Here we investigated a key role of Wnt signaling in the molecular regulation of ZLI positioning and Shh expression, using experimental embryology in ovo in the chick. Early Wnt expression in the ZLI regulates Gli3 and L-fng to generate a permissive territory in which Shh is progressively induced by planar signals of the basal plate. Introduction Vieira et al., 2005; Guinazu et al., 2007). However, Six3 is not The zona limitans intrathalamica (ZLI) is a neuroepithelial do- required for the formation of the mammalian ZLI (Lavado et al., main intercalated between the prethalamus and the thalamus in 2008). -
EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area
bioRxiv preprint doi: https://doi.org/10.1101/442111; this version posted October 12, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. EZH2 is essential for fate determination in the mammalian Isthmic area Iris Wever1, Cindy M.R.J. Wagemans1 and Marten P. Smidt1 1Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands bioRxiv preprint doi: https://doi.org/10.1101/442111; this version posted October 12, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including Polycomb Repressive Complex (PRC) 2. EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and trimethylation of lysine 27 of histone 3 (H3K27Me3), the chromatin mark associated with gene silencing. Loss-of-function studies of Ezh2, the catalytic subunit of PRC2, have shown that PRC2 plays a role in regulating developmental transitions of neuronal progenitor cells; from self-renewal to differentiation and the neurogenic-to-gliogenic fate switch. To further address the function of EZH2 and H3K27me3 during neuronal development we generated a conditional mutant in which Ezh2 was removed in the mammalian isthmic (mid-hindbrain) region from E10.5 onward. Loss of Ezh2 changed the molecular coding of the anterior ventral hindbrain leading to a fate switch and the appearance of ectopic dopaminergic neurons. -
Experimental Study of MAP Kinase Phosphatase-3 (Mkp3) Expression in the Chick Neural Tube in Relation to Fgf8 Activity
Brain Research Reviews 49 (2005) 158–166 www.elsevier.com/locate/brainresrev Review Experimental study of MAP kinase phosphatase-3 (Mkp3) expression in the chick neural tube in relation to Fgf8 activity Claudia Vieira, Salvador MartinezT Neuroscience Institute UMH-CSIC, University Miguel Hernandez, N-332, Km 87, E-03550 San Juan de Alicante, Spain Accepted 8 December 2004 Available online 7 April 2005 Abstract Mitogen-activated protein kinase (MAPK) pathways are well known to be involved in signal transduction from extracellular to intracellular compartments in all eukaryotes. The activation of this cascade will have an effect on cell proliferation, differentiation, and apoptosis. In this study, we describe the cloning of the chick Mkp3 gene that is highly homologous to the mammalian gene and are both expressed in several embryo regions with demonstrated morphogenetic activity. In early developmental stages, Mkp3 and Fgf8 have similar expression patterns. Differences in the activation of Mkp3 transcription in the isthmus and the repression with FGF receptor inhibition suggest that Fgf8 protein controls Mkp3 transcription. Ectopically, expression of Fgf8 protein induces Mkp3 in a short period of time in the diencephalon, indicating a positive regulation of Mkp3 by Fgf8. Moreover, we show a distinct tissue competence to express Mkp3 rostrally and caudally to the zona limitans intrathalamica (ZLI). D 2005 Elsevier B.V. All rights reserved. Theme: Development and regeneration Topic: Pattern formation, compartments, and boundaries Keywords: Mid–hindbrain boundary; Isthmic organizer; Zona limitans intrathalamica; Mkp3; Fgf8; MAPK Contents 1. Introduction........................................................... 159 2. Materials and methods ..................................................... 159 2.1. Cloning of a chick homologue of Mkp3 ....................................... -
CRISPR Gene Editing Reveals Genetic Compensation As a Mechanism for Phenotypic Disjunction of Morphants and Mutants
International Journal of Molecular Sciences Review Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants Cristy M. Salanga 1,2 and Matthew C. Salanga 2,* 1 Office of the Vice President for Research, Northern Arizona University, Flagstaff, AZ 86011, USA; [email protected] 2 Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA * Correspondence: [email protected] Abstract: Forward genetic screens have shown the consequences of deleterious mutations; however, they are best suited for model organisms with fast reproductive rates and large broods. Furthermore, investigators must faithfully identify changes in phenotype, even if subtle, to realize the full benefit of the screen. Reverse genetic approaches also probe genotype to phenotype relationships, except that the genetic targets are predefined. Until recently, reverse genetic approaches relied on non-genomic gene silencing or the relatively inefficient, homology-dependent gene targeting for loss-of-function generation. Fortunately, the flexibility and simplicity of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has revolutionized reverse genetics, allowing for the precise mutagenesis of virtually any gene in any organism at will. The successful integration of insertions/deletions (INDELs) and nonsense mutations that would, at face value, produce the Citation: Salanga, C.M.; Salanga, expected loss-of-function phenotype, have been shown to have little to no effect, even if other M.C. Genotype to Phenotype: methods of gene silencing demonstrate robust loss-of-function consequences. The disjunction CRISPR Gene Editing Reveals Genetic between outcomes has raised important questions about our understanding of genotype to phenotype Compensation as a Mechanism for Phenotypic Disjunction of Morphants and highlights the capacity for compensation in the central dogma.