DOCSLIB.ORG

Genetic Technologies for Building a Better Mouse

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic Technologies for Building a Better Mouse Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW A most formidable arsenal: genetic technologies for building a better mouse James F. Clark,1 Colin J. Dinsmore,1 and Philippe Soriano Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mt. Sinai, New York, New York 10029, USA The mouse is one of the most widely used model organ- scribing Mendelian inheritance for mouse coat color char- isms for genetic study. The tools available to alter the acteristics (Cuénot 1902). Mendel himself had started mouse genome have developed over the preceding decades down this same road fifty years earlier, only for his bishop from forward screens to gene targeting in stem cells to the to snuff out the nascent breeding program because a monk recent influx of CRISPR approaches. In this review, we had no business, frankly, breeding (Paigen 2003). first consider the history of mice in genetic study, the Following Cuénot’s papers (Cuénot 1902), genetic re- development of classic approaches to genome modifica- search using the mouse began in earnest, often through tion, and how such approaches have been used and im- the study of spontaneous mouse mutants. One line of re- proved in recent years. We then turn to the recent surge search further explored the complicated genetics of pig- of nuclease-mediated techniques and how they are chang- mentation and the sometimes-surprising coincident ing the field of mouse genetics. Finally, we survey com- phenotypes. The Dominant white spotting allele W (an al- mon classes of alleles used in mice and discuss how lele of the receptor tyrosine kinase Kit) was found to affect they might be engineered using different methods. not only pigmentation but also hematopoiesis and fertili- ty, for instance. Another line focused on the genetic basis of other variable traits such as histocompatibility, sex de- termination and X-inactivation, and classic studies of tail length and the T locus (Silver 1995). Perhaps the most con- The origins of mice as a genetic system sequential endeavor, however, was the effort to under- stand the relationship between genetics and cancer, as The house mouse, Mus musculus, has been a tool of genet- this led to the establishment of many of today’s inbred ic inquiry for well over a century. A case can be made that mouse strains as well as the founding of mouse genetic re- the tradition dates back even further to 18th century Japan search centers such as the Jackson Laboratory in 1929, and China where local mouse and rat fanciers wrote guide- Oak Ridge in 1943, MRC Harwell in 1947, and the Nation- books on how to raise these animals, including detailed al Institute of Genetics in Japan in 1949 (Silver 1995). breeding strategies to obtain particular coat patterns Alongside research using laboratory inbred strains, study (Tokuda 1935; Kuramoto 2011). The hobby of mouse fan- of wild mouse populations led to important insights in im- cying was exported to England and from there to the Unit- munity, cancer, and adaptation (Phifer-Rixey and Nach- ed States, where fancier stocks formed the basis of many man 2015). Modern genomic techniques now couple modern inbred strains (Morse 1978). Nevertheless, the wild populations’ variations and selective pressures with first genetic experiment using mice may have been per- molecular precision (Harr et al. 2016; Barrett et al. 2019). formed in 1887 by August Weismann, who surgically re- A full accounting of the history of mouse genetic research moved the tails of mice, bred them, and found offspring is beyond the scope of this article, but has been the subject with tails of normal length (Weismann 1889). This result of several excellent books and reviews (Russell 1985; Sil- challenged Lamarckian inheritance and led Weismann to ver 1995; Paigen 2003; García-García 2020). propose the germ theory of inheritance, which stated that Even with these impressive genetic bona fides, the true hereditary information was transmitted only through potential of mouse genetics lies in the ability of the re- germ cells: the sperm and egg. The origin of mice as a mod- searcher to modify the mouse genome. This ability, along el system for genetic analysis, with intrinsic variable and with the fact that mice are mammals with substantial ge- heritable traits worthy of study, dates to 1902 when netic similarity to humans, has made mice a favorite Lucien Cuénot published the first in a series of papers de- © 2020 Clark et al. This article is distributed exclusively by Cold Spring [Keywords: gene targeting; CRISPR; mice; genetics; transgenesis] Harbor Laboratory Press for the first six months after the full-issue publi- 1These authors contributed equally to this work. cation date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After Corresponding author: [email protected] six months, it is available under a Creative Commons License (Attribu- Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.342089. tion-NonCommercial 4.0 International), as described at http://creative- 120. commons.org/licenses/by-nc/4.0/. 1256 GENES & DEVELOPMENT 34:1256–1286 Published by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/20; www.genesdev.org Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Building a better mouse system for understanding the genetic underpinnings of been used to better understand topics ranging from mouse mammalian development and human disease (Rosenthal development (Kasarskis et al. 1998; Nolan et al. 2000), to and Brown 2007). Indeed, as of July 28, 2020, there were circadian rhythms (Vitaterna et al. 1994), congenital heart 64,204 mutant mouse alleles listed in the Mouse Genome disease (Li et al. 2015), and the genetic basis of sleep Informatics (MGI) database. The tools available to gener- (Miyoshi et al. 2019), among many others. ate these alleles have been steadily expanded from forward The precursor to mouse genetic screens arose from an genetic screens, to viral and gene trap-mediated approach- interest in cancer and the effects of atomic radiation on es, as well as classic homologous recombination-based mammals. These effects were investigated using mice, targeting in mouse embryonic stem cells (mESCs) that principally at the Oak Ridge National Laboratory in Oak served as the basis for the myriad knockout, knock-in, Ridge, Tennessee, and the MRC Radiobiological Research knockdown, conditional, and lineage-tracing mouse mod- Unit in Harwell, England. This research generated numer- els that now exist. More recently, nuclease-mediated ous mutant mouse strains, but because X-rays induce dou- technologies such as CRISPR/Cas have led to a second ex- ble-stranded breaks (DSBs) in DNA, the approach often plosion of techniques. These not only promise an easier, caused large deletions and chromosomal rearrangements more efficient means to traditional genetic ends, but are that affected multiple genes, making interpretation of also opening the door to ways of modifying the genome the mutant phenotypes difficult (Silver 1995). Radiation that were previously impractical or impossible with clas- has been supplanted by chemical mutagenesis with the sical techniques. DNA alkylating agent N-ethyl-N-nitrosourea (ENU), which is more mutagenic than X-rays (Russell et al. 1979) and more likely to result in point mutations (Popp Forward genetic screens et al. 1983). Because screening large numbers of mice in the G3 generation is so time- and labor-intensive, there Forward genetic screens involve germline mutagenesis are several modified approaches that allow for recovery and subsequent breeding of male mice to obtain a collec- of recessive mutations in the G2 generation. Specifically, tion of novel mutations. Offspring in the first generation modifier (enhancer or suppressor) and noncomplementa- (termed G1, the result of crossing a mutagenized mouse tion screens are performed by crossing G1 mutants with with a wild-type female) can be immediately screened an existing mutant strain and assaying for a modified phe- for dominant mutations giving rise to a phenotype of in- notype or failure to complement. This usually identifies terest. For recessive mutations, G1 males can be crossed new genes that genetically interact with the gene of inter- with a wild-type female and then any G2 females are est or novel alleles of the same gene, respectively. Dele- crossed back to their G1 father to generate homozygous tion screens, in which G1 males are crossed to females offspring in the third generation (G3). After identifying carrying a deletion of a chromosomal interval, facilitate mutant lines with the desired phenotype, the underlying rapid identification of mutations in this region. Finally, mutation is identified. This was traditionally achieved balancer screens, most famous from the world of fly genet- by time-consuming genetic mapping but can now be re- ics, can also be performed in mice even though the num- solved through genome sequencing, greatly accelerating ber of existing balancer chromosomes is limited (Zheng the overall process (Wang et al. 2015; Geister et al. et al. 1999). These involve crossing mutagenized males 2018). The advantage of genetic screens is that mutations to mice carrying a balancer chromosome, which has the are generated semi-randomly throughout the genome, so following features: one or a series of tandem chromosomal screens are unbiased with respect to the underlying muta- inversions that suppress recombination within the region, tion and can reveal unexpected genotype–phenotype con- a dominant visible trait such as coat color, and often a re- nections. One reason for this is that such screens can cessive lethal mutation (Zheng et al. 1999; Ye et al. 2016). identify many genes important for a given process that This combination of factors allows efficient breeding have not yet been investigated or linked to that process.
Load more

Recommended publications
  • Prime Editing €“ an Update on the Field
    Gene Therapy (2021) 28:396–401 https://doi.org/10.1038/s41434-021-00263-9 PERSPECTIVE Prime editing – an update on the field 1,2 3 Janine Scholefield ● Patrick T. Harrison Received: 12 January 2021 / Revised: 15 April 2021 / Accepted: 5 May 2021 / Published online: 24 May 2021 © The Author(s) 2021. This article is published with open access At Gene Therapy, we are continually monitoring the land- containing RNA template as a contiguous extension of the scape of research, noting those technologies which advance guide RNA (known as the pegRNA), and M-MLV reverse the goal of clinical translation of the field. In one of the transcriptase (RT) fused to the C terminus of Cas9 (H840A) most exciting ‘needle-shifting’ gene editing publications nickase. Use of the Cas9 nickase avoids the formation of a published in 2019, David Liu et al., (who pioneered base DSB, and simply cuts the non-complementary strand of editing; BE [1]), developed ‘Prime editing (PE) [2]’, erasing the DNA three bases upstream of the PAM site. This several limits of CRISPR that have caused bottlenecks in its exposes a DNA flap with a 3’ OH group which binds to the therapeutic and biotechnological applicability. Traditional primer binding site (PBS) of the RNA template, serving as a gene editing strategies directing specific changes to the primer for RT, which extends the 3’ flap by copying the edit 1234567890();,: 1234567890();,: genome sequence itself largely reply on a common step – sequence of the pegRNA (Fig. 1). Despite this extended 3’ creating a double-strand break (DSB) to attract and exploit flap being thermodynamically less likely to hybridise to the the DNA repair pathway machinery in executing the desired unedited complementary strand compared to the unedited 5’ repair.
    [Show full text]
  • Downloaded from [266]
    Patterns of DNA methylation on the human X chromosome and use in analyzing X-chromosome inactivation by Allison Marie Cotton B.Sc., The University of Guelph, 2005 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies (Medical Genetics) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) January 2012 © Allison Marie Cotton, 2012 Abstract The process of X-chromosome inactivation achieves dosage compensation between mammalian males and females. In females one X chromosome is transcriptionally silenced through a variety of epigenetic modifications including DNA methylation. Most X-linked genes are subject to X-chromosome inactivation and only expressed from the active X chromosome. On the inactive X chromosome, the CpG island promoters of genes subject to X-chromosome inactivation are methylated in their promoter regions, while genes which escape from X- chromosome inactivation have unmethylated CpG island promoters on both the active and inactive X chromosomes. The first objective of this thesis was to determine if the DNA methylation of CpG island promoters could be used to accurately predict X chromosome inactivation status. The second objective was to use DNA methylation to predict X-chromosome inactivation status in a variety of tissues. A comparison of blood, muscle, kidney and neural tissues revealed tissue-specific X-chromosome inactivation, in which 12% of genes escaped from X-chromosome inactivation in some, but not all, tissues. X-linked DNA methylation analysis of placental tissues predicted four times higher escape from X-chromosome inactivation than in any other tissue. Despite the hypomethylation of repetitive elements on both the X chromosome and the autosomes, no changes were detected in the frequency or intensity of placental Cot-1 holes.
    [Show full text]
  • PIR Brochure
    Protein Information Resource Integrated Protein Informatics Resource for Genomic & Proteomic Research For four decades the Protein Information Resource (PIR) has provided databases and protein sequence analysis tools to the scientific community, including the Protein Sequence Database, which grew out from the Atlas of Protein Sequence and Structure, edited by Margaret Dayhoff [1965-1978]. Currently, PIR major activities include: i) UniProt (Universal Protein Resource) development, ii) iProClass protein data integration and ID mapping, iii) PIRSF protein pir.georgetown.edu classification, and iv) iProLINK protein literature mining and ontology development. UniProt – Universal Protein Resource What is UniProt? UniProt is the central resource for storing and UniProt (Universal Protein Resource) http://www.uniprot.org interconnecting information from large and = + + disparate sources and the most UniProt: the world's most comprehensive catalog of information on proteins comprehensive catalog of protein sequence and functional annotation. UniProt Knowledgebase UniProt Reference UniProt Archive (UniProtKB) Clusters (UniRef) (UniParc) When to use UniProt databases Integration of Swiss-Prot, TrEMBL Non-redundant reference A stable, and PIR-PSD sequences clustered from comprehensive Use UniProtKB to retrieve curated, reliable, Fully classified, richly and accurately UniProtKB and UniParc for archive of all publicly annotated protein sequences with comprehensive or fast available protein comprehensive information on proteins. minimal redundancy and extensive sequence searches at 100%, sequences for Use UniRef to decrease redundancy and cross-references 90%, or 50% identity sequence tracking from: speed up sequence similarity searches. TrEMBL section UniRef100 Swiss-Prot, Computer-annotated protein sequences TrEMBL, PIR-PSD, Use UniParc to access to archived sequences EMBL, Ensembl, IPI, and their source databases.
    [Show full text]
  • Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
    ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database.
    [Show full text]
  • 1 Supporting Information for a Microrna Network Regulates
    Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia.
    [Show full text]
  • Loss of BCL-3 Sensitises Colorectal Cancer Cells to DNA Damage, Revealing A
    bioRxiv preprint doi: https://doi.org/10.1101/2021.08.03.454995; this version posted August 4, 2021. 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. Title: Loss of BCL-3 sensitises colorectal cancer cells to DNA damage, revealing a role for BCL-3 in double strand break repair by homologous recombination Authors: Christopher Parker*1, Adam C Chambers*1, Dustin Flanagan2, Tracey J Collard1, Greg Ngo3, Duncan M Baird3, Penny Timms1, Rhys G Morgan4, Owen Sansom2 and Ann C Williams1. *Joint first authors. Author affiliations: 1. Colorectal Tumour Biology Group, School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK 2. Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden Glasgow, G61 1BD UK 3. Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN UK 4. School of Life Sciences, University of Sussex, Sussex House, Falmer, Brighton, BN1 9RH UK 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.03.454995; this version posted August 4, 2021. 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 (250 words) Objective: The proto-oncogene BCL-3 is upregulated in a subset of colorectal cancers (CRC) and increased expression of the gene correlates with poor patient prognosis. The aim is to investigate whether inhibiting BCL-3 can increase the response to DNA damage in CRC.
    [Show full text]
  • Update on Genome Completion and Annotations
    UPDATE ON GENOME COMPLETION AND ANNOTATIONS Update on genome completion and annotations: Protein Information Resource Cathy Wu1and Daniel W. Nebert2* 1Director of PIR, Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC, USA 2Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 558 4347; Fax: þ1 513 558 3562; E-mail: [email protected] Date received (in revised form): 11th January 2004 Abstract The Protein Information Resource (PIR) recently joined the European Bioinformatics Institute (EBI) and Swiss Institute of Bioinformatics (SIB) to establish UniProt — the Universal Protein Resource — which now unifies the PIR, Swiss-Prot and TrEMBL databases. The PIRSF (SuperFamily) classification system is central to the PIR/UniProt functional annotation of proteins, providing classifications of whole proteins into a network structure to reflect their evolutionary relationships. Data integration and associative studies of protein family, function and structure are supported by the iProClass database, which offers value-added descriptions of all UniProt proteins with highly informative links to more than 50 other databases. The PIR system allows consistent, rich and accurate protein annotation for all investigators. Keywords: protein web sites, protein family, functional annotation Introduction system.2 This framework is supported by the iProClass integrated database of protein family, function and structure.3 The high-throughput genome projects have resulted in a rapid iProClass offers value-added descriptions of all UniProt accumulation of genome sequences for a large number of proteins and has highly informative links to more than 50 organisms.
    [Show full text]
  • A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.05.136192; this version posted June 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Contreras et al., A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis Ximena Contreras1, Amarbayasgalan Davaatseren1, Nicole Amberg1, Andi H. Hansen1, Johanna Sonntag1, Lill Andersen2, Tina Bernthaler2, Anna Heger1, Randy Johnson3, Lindsay A. Schwarz4,5, Liqun Luo4, Thomas Rülicke2 & Simon Hippenmeyer1,6,# 1 Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria 2 Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria 3 Department of Biochemistry and Molecular Biology, University of Texas, Houston, TX 77030, USA 4 HHMI and Department of Biology, Stanford University, Stanford, CA 94305, USA 5 Present address: St. Jude Children’s Research Hospital, Memphis, TN 38105, USA 6 Lead contact #Correspondence and requests for materials should be addressed to S.H. ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.05.136192; this version posted June 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Contreras et al., SUMMARY Mosaic Analysis with Double Markers (MADM) offers a unique approach to visualize and concomitantly manipulate genetically-defined cells in mice with single-cell resolution.
    [Show full text]
  • Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration
    Neuron Article Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration Simon Hippenmeyer,1,* Yong Ha Youn,2 Hyang Mi Moon,2,3 Kazunari Miyamichi,1 Hui Zong,1,5 Anthony Wynshaw-Boris,2,4 and Liqun Luo1,* 1Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA 2Department of Pediatrics and Institute for Human Genetics 3Biomedical Sciences Graduate Program 4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA 5Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA *Correspondence: [email protected] (S.H.), [email protected] (L.L.) DOI 10.1016/j.neuron.2010.09.027 SUMMARY studied. Cortical layering occurs in an ‘‘inside-out’’ fashion whereby earlier born neurons occupy deep layers and succes- Coordinated migration of newly born neurons to their sively later born neurons settle in progressively upper layers (An- prospective target laminae is a prerequisite for neural gevine and Sidman, 1961; Rakic, 1974). Upon radial glia progen- circuit assembly in the developing brain. The evolu- itor cell (RGPC)-mediated neurogenesis, newborn migrating tionarily conserved LIS1/NDEL1 complex is essential cortical projection neurons are bipolar-shaped in the ventricular for neuronal migration in the mammalian cerebral zone (VZ) but then convert to a multipolar morphology within the cortex. The cytoplasmic nature of LIS1 and NDEL1 subventricular zone (SVZ) and migrate into the intermediate zone (IZ). A switch from the multipolar state back to a bipolar proteins suggest that they regulate neuronal migra- morphology precedes radial glia-guided locomotion of projec- tion cell autonomously.
    [Show full text]
  • Activation of Aurora-A Is Essential for Neuronal Migration Via Modulation of Microtubule Organization
    11050 • The Journal of Neuroscience, August 8, 2012 • 32(32):11050–11066 Cellular/Molecular Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization Takako Takitoh,1 Kanako Kumamoto,1 Chen-Chi Wang,2,4 Makoto Sato,2,3,4 Shiori Toba,1 Anthony Wynshaw-Boris,5 and Shinji Hirotsune1 1Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan, 2Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, 3Child Development Research Center, Graduate School of Medical Sciences, University of Fukui, 4Research and Education Program for Life Science, University of Fukui, Fukui 910-1193, Japan, and 5Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, School of Medicine, San Francisco, California 94143 Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an “inside-out” gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A–NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition, in utero injection of the Aurora-A kinase-dead mutant provoked defective migra- tion of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration.
    [Show full text]
  • Atlas Journal
    Atlas of Genetics and Cytogenetics in Oncology and Haematology Home Genes Leukemias Tumors Cancer prone Deep Insight Case Reports Portal Journals Teaching X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA Atlas Journal Atlas Journal versus Atlas Database: the accumulation of the issues of the Journal constitutes the body of the Database/Text-Book. TABLE OF CONTENTS Volume 13, Number 7, July 2009 Previous Issue / Next Issue Genes ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1) (9q34.1) - updated. Ali G Turhan. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 757-766. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/ABL.html BCL2L12 (BCL2-like 12 (proline-rich)) (19q13.3). Christos Kontos, Hellinida Thomadaki, Andreas Scorilas. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 767-771. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/BCL2L12ID773ch19q13.html BCR (Breakpoint cluster region) (22q11.2) - updated. Ali G Turhan. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 772-779. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/BCR.html ENAH (enabled homolog (Drosophila)) (1q42.12). Paola Nisticò, Francesca Di Modugno. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 780-785. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/ENAHID44148ch1q42.html FGFR2 (fibroblast growth factor receptor 2) (10q26.13). Masaru Katoh. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 786-799. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/FGFR2ID40570ch10q26.html MAPK6 (mitogen-activated protein kinase 6) (15q21.2). Sylvain Meloche. Atlas Genet Cytogenet Oncol Haematol 2009; 13 (7): 800-804.
    [Show full text]
  • Humankind 2.0: the Technologies of the Future 6. Biotech
    Humankind 2.0: The Technologies of the Future 6. Biotech Piero Scaruffi, 2017 See http://www.scaruffi.com/singular/human20.html for the full text of this discussion A brief History of Biotech 1953: Discovery of the structure of the DNA 2 A brief History of Biotech 1969: Jon Beckwith isolates a gene 1973: Stanley Cohen and Herbert Boyer create the first recombinant DNA organism 1974: Waclaw Szybalski coins the term "synthetic biology” 1975: Paul Berg organizes the Asilomar conference on recombinant DNA 3 A brief History of Biotech 1976: Genentech is founded 1977: Fred Sanger invents a method for rapid DNA sequencing and publishes the first full DNA genome of a living being Janet Rossant creates a chimera combining two mice species 1980: Genentech’s IPO, first biotech IPO 4 A brief History of Biotech 1982: The first biotech drug, Humulin, is approved for sale (Eli Lilly + Genentech) 1983: Kary Mullis invents the polymerase chain reaction (PCR) for copying genes 1986: Leroy Hood invents a way to automate gene sequencing 1986: Mario Capecchi performs gene editing on a mouse 1990: William French Anderson’s gene therapy 1990: First baby born via PGD (Alan Handyside’s lab) 5 A brief History of Biotech 1994: FlavrSavr Tomato 1994: Maria Jasin’s homing endonucleases for genome editing 1996: Srinivasan Chandrasegaran’s ZFN method for genome editing 1996: Ian Wilmut clones the first mammal, the sheep Dolly 1997: Dennis Lo detects fetal DNA in the mother’s blood 2000: George Davey Smith introduces Mendelian randomization 6 A brief History of Biotech
    [Show full text]