DOCSLIB.ORG

Gene and Protein Interactions in Limb Development : the Case of Msx and Gli3 Mathura Shanmugasundaram

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Gene and protein interactions in limb development : the case of Msx and Gli3 Mathura Shanmugasundaram To cite this version: Mathura Shanmugasundaram. Gene and protein interactions in limb development : the case of Msx and Gli3. Development Biology. Université Pierre et Marie Curie - Paris VI, 2015. English. NNT : 2015PA066279. tel-01368052 HAL Id: tel-01368052 https://tel.archives-ouvertes.fr/tel-01368052 Submitted on 19 Sep 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Thèse de doctorat de l’Université Paris VI - Pierre et Marie Curie Pour obtenir le titre de Docteur de l’Université Paris VI Ecole Doctorale: Complexité du Vivant Spécialité: Biologie du développement Soutenue le 17 September 2015 par Mathura SHANMUGASUNDARAM Gene And Protein Interactions In Limb Development: The Case Of Msx And Gli3 Devant le jury composé de: Dr. Sylvie Schneider-Maunoury Président du Jury Dr. Bénédicte B Durand Rapporteur Dr. Marian Ros Rapporteur Dr. Malcolm Logan Examinateur Dr. Benoît Robert Directeur de thèse Gene and protein interactions in limb development: The case of Msx and Gli3 “What can be more curious than that the hand of the man formed for grasping, that of a mole, for digging, the leg of a horse, the paddle of a porpoise and the wing of a bat, should all be constructed on the same pattern and should include similar bones and in the same relative positions?” Charles Darwin, Origin of Species. Mathura Shanmugasundaram 2 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 Acknowledgements Mathura Shanmugasundaram 3 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 Acknowledgements I would like to sincerely acknowledge and convey my heartfelt gratitude and thanks to Benoît Robert, my mentor and advisor who not only gave me the wonderful opportunity to work in the Genetic and Molecular Morphogenesis Unit at Institut Pasteur, Paris but also supervised and guided me throughout the last four years. For all this and more, I dedicate this work to my guru, Benoit, without whom I would not have achieved this. Thank you for all your support and for believing in me. I would like to extend my gratitude and thanks to Yvan Lallemand, for your unwavering support and your kind gestures of advice and scientific conversations. To Pascal, for being an amazing technician. To Juliane, for your support and advice throughout the last year. To Didier, for your daily dose of entertainment and support as well as for generously sharing your wonderful office with me. I must also acknowledge many others who have made my stay in Institut Pasteur and Paris a wonderful experience. Thank you Clémire Cimper for being there with your motherly affection. Thank you Gaya and Julie for your beautiful friendship and for supporting me throughout my journey and for helping me adapt to France and it’s culture. A special thanks to Swetha for your moral support and to all my “Friday-lunch” mates. A big thanks to the department of developmental and stem cell biology for being an awesome and vibrant community. Thanks folks! I would also like to acknowledge the International Paris- Pasteur University (PPU) Program for their support and guidance throughout the years. And of course, last but not least, thank you to my dear family for being there throughout everything. For this and more, this is for all of you. I am certainly going to miss you all. Cette thèse conclut ma grande aventure Française. Je souhaite exprimer mon infinie gratitude à Benoit Robert sans qui ce travail n’aurait pas pu aboutir. Je veux remercier Yvan Lallemand pour son encadrement scientifique. Didier Montarras, je vous remercie pour vos conseils toujours précieux, chaque journée a été agrèable à vos côtés. Merci aussi, à Pascal et Catherine pour leur aide technique. Merci Clémire, Julie et Gaya pour être toujours là pour moi. Un grand merci à Maxime, pour tout. Je souhaite exprimer ma reconnaissance à tous ceux qui de près ou de loin m’ont aidé durant mes quatre années Françaises. Vous me manquerez, tous! Cette thèse est pour vous tous. Mathura Shanmugasundaram 4 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 Msx interacts with Gli3 in modulating limb morphogenesis Abstract The vertebrate limb is a paradigmatic model for morphogenesis. The anteroposterior (AP) growth and patterning of the limb bud rely on an intricate regulatory genetic network involving many genetic players such as Hox genes, Sonic hedgehog (Shh), Gli3. Shh is produced in a posterior region of the limb mesoderm and acts as a morphogen along the AP axis. It regulates both digit number and identity of different AP positions. As the main function of Shh is to prevent proteolysis of Gli3FL into Gli3R, Gli3R thereby concentrates anteriorly which notably is also the place where apoptosis takes place. In the mouse, paradoxically, despite a quasi-symmetrical expression profile, Msx1/2 null mutants show systematic anterior defects with an overgrowth in the anterior limb domain, resulting in anterior polydactyly. Both Gli3 and Msx mutant limb defects are concentrated anteriorly in a similar fashion suggesting an interaction between these genes and a possible role of this interaction in AP patterning in the limb bud as well as dysregulation of apoptosis. Indeed, we demonstrate interactions between Msx and Gli3 genes and even proteins. Mutations of Msx and Gli3 both result in anterior polydactylous phenotypes and similar loss of anterior apoptotic domains. This morphological analysis is associated with a search for common Gli3 and Msx transcriptional targets and partners in an attempt to link gene activity with changes in cell physiology that underlie morphogenesis. We have performed a differential transcriptome (RNA-Seq) on whole limb buds of Msx1-/-Msx2-/-, which has led us to narrow down on a number of potential common targets of Gli3 and Msx. Our results demonstrate that Msx and Gli3 work together in regulating the anterior posterior axis of limb development, independent of Shh. Mathura Shanmugasundaram 5 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 Abbreviation List A Alanine ADH Alcohol dehydrogenase AER Apical Ectodermal Ridge AP Anterior-Posterior BMP Bone morphogenetic protein Bmpr Bone morphogenetic protein receptor CI Clavicle Ci Cubitus Interruptus CRD Cysteine-rich domain dhh Desert hedgehog DNA Deoxyribo nucleic acid DV Dorsal- Ventral Eh1 Engrailed homology domain 1 EN-1 Engrailed 1 FGF Fibroblast Growth Factor FL Forelimb fpp Foyer préaxial primaire G Glycine Gli3A Gli3 Activated form Gli3FL GLi3 Full form Gli3R Gli3 repressor (truncated form) GPCR G-protein-coupled-like receptors Grg Groucho Hh Hedgehog Hhat Hedgehog acyl-transferase HL Hindlimb HTH Helix-Turn-Helix Hu Humerus ICD Interdigital Cell Death Ihh Indian Hedgehog IM Intermediate mesoderm kd Kilo-daltons (unit) LPM Lateral plate mesoderm msh Muscle segment homeobox P Proline PD Proximal-distal Pdn Polydactyly Nagoya PKA Protein kinase A Mathura Shanmugasundaram 6 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 Ptch Patched PZ Progress Zone RA Retionic acid Ra Radius Raldh Retinaldehyde dehydrogenases RDH Retinol dehydrogenase Sc Scapula Shh Sonic hedgehog Skn Skinny hedgehog Smo Smoothened Tbx T-box transcription factors Ul Ulna ZPA Zone of polarising activity Mathura Shanmugasundaram 7 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 CONTENTS PAGE Acknowledgements 3 Abstract 5 Abbreviations 6 INTRODUCTION Part A Limb structure and development 10 1 The limb as a model system 11 1.1 Limb initiation 11 1.2 The difficult case of Retionic Acid (RA) 13 1.3 The three axes of limb development 14 1.4 Early limb development 17 1.5 PD patterning: Old and new models 19 1.6 Dorsoventral (DV) axis 23 1.6.1 DV patterning 23 1.6.2 DV determination and AER development 25 1.7 Anterior-Posterior (AP) patterning 26 1.8 The Hedgehog (Hh) pathway 29 1.8.1 Shh auto modification and signalling 29 1.8.2 Hh receptors 32 1.9 Transcriptional targets of Shh signalling: Gli transcription factors 33 1.9.1 Gli expression during limb development 35 1.9.2 Gli processing 35 1.9.3 Shh in AP polarity and digit patterning 37 Part B Msx genes 2 A brief introduction to Msx genes 43 2.1 The discovery of Msx genes 44 2.1.1 Msx genes are homeobox genes 45 2.1.2 The Msx gene family 46 2.1.3 Msx in evolution 47 2.2 Msx genes at a molecular level 48 2.2.1 Chromosomal localization 48 2.2.2 Msx conserved structure 48 2.3 Msx gene expressions in vertebrates 51 2.4 Msx mutations 2.4.1 Msx1 mutation 53 2.4.1.1 Msx1 mutations in mice 53 2.4.1.2 Msx1 mutation in humans 55 Mathura Shanmugasundaram 8 Doctoral Thesis, Institut Pasteur 2015 Gene and protein interactions in limb development: The case of Msx and Gli3 2.4.2 Msx2 mutation 56 2.4.2.1 Msx2 mutations in mice 56 2.4.2.2 Msx2 mutations in humans 57 2.5 Msx functions 59 2.5.1 Transcriptional activity of Msx 60 2.6 Msx and apoptosis 62 2.6.1 Apoptosis in the limb: Interdigital cell death (ICD) 62 2.6.2 Apoptosis and the anterior digit: The thumb 64 2.6.3 Msx in anterior apoptosis 65 2.7 Msx and Epithelial- Mesenchymal interactions (EMI) 66 2.8 Msx in proliferation, differentiation and regeneration 67 2.9 Msx at the crossroads of limb development 71 3.
Recommended publications
  • Wnt Signalling During Limb Development

    Wnt Signalling During Limb Development

    Int. J. Dev. Biol. 46: 927-936 (2002) Wnt signalling during limb development VICKI L. CHURCH and PHILIPPA FRANCIS-WEST* Department of Craniofacial Development, King’s College London, Guy’s Hospital, London, UK ABSTRACT Wnts control a number of processes during limb development - from initiating outgrowth and controlling patterning, to regulating cell differentiation in a number of tissues. Interactions of Wnt signalling pathway components with those of other signalling pathways have revealed new mechanisms of modulating Wnt signalling, which may explain how different responses to Wnt signalling are elicited in different cells. Given the number of Wnts that are expressed in the limb and their ability to induce differential responses, the challenge will be to dissect precisely how Wnt signalling is regulated and how it controls limb development at a cellular level, together with the other signalling pathways, to produce the functional limb capable of co- ordinated precise movements. KEY WORDS: Wnt, limb, development, chondrogenesis, myogenesis The Wnt Gene Family is found in the others (Cadigan and Nusse, 1997). The frizzled receptors can function together with the LRP co-receptors, which The Wnt family of secreted glycosylated factors consists of 22 are single transmembrane proteins containing LDL receptor re- members in vertebrates which have a range of functions during peats, two frizzled motifs and four EGF type repeats in the development from patterning individual structures to fine tuning at extracellular domain (reviewed by Pandur and Kühl, 2001; also see a cellular level controlling cell differentiation, proliferation and Roszmusz et al., 2001). The LRPs, which include the vertebrate survival. The founding members of this family are the Drosophila genes LRP4, -5 and -6 and the Drosophila gene arrow, form a segment polarity gene Wingless (Wg), required for wing develop- complex with frizzled in a Wnt-dependent manner and signal in the ment, together with Wnt1 (originally named int-1) in the mouse.
  • Masking Techniques

    Masking Techniques

    Available online at www.sciencedirect.com SCI ENCE(C$ DIRECT Developmental Biology 273 (2004) 361-372 www.elsevier.com/locate/ydbio The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth Anne M. Bouleta, Anne M. Moonb,c, Benjamin R. Arenkiela, Mario R. Capecchi3’* ^Department of Human Genetics, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA bProgram in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA cDepartment of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA Received for publication 12 May 2004, revised 16 June 2004, accepted 21 June 2004 Abstract Although numerous molecules required for limb bud formation have recently been identified, the molecular pathways that initiate this process and ensure that limb formation occurs at specific axial positions have yet to be fully elucidated. Based on experiments in the chick, Fg/8 expression in the intermediate mesoderm (IM) has been proposed to play a critical role in the initiation of limb bud outgrowth via restriction of Fgfl 0 expression to the appropriate region of the lateral plate mesoderm. Contrary to the outcome predicted by this model, ablation of Fgf8 expression in the intermediate mesoderm before limb bud initiation had no effect on initial limb bud outgrowth or on the formation of normal limbs. When their expression patterns were first elucidated, both Fgf4 and Fg/8 were proposed to mediate critical functions of the apical ectodermal ridge (AER), which is required for proper limb bud outgrowth.
  • Interaction Network of Immune‑Associated Genes Affecting the Prognosis of Patients with Glioblastoma

    Interaction Network of Immune‑Associated Genes Affecting the Prognosis of Patients with Glioblastoma

    EXPERIMENTAL AND THERAPEUTIC MEDICINE 21: 61, 2021 Interaction network of immune‑associated genes affecting the prognosis of patients with glioblastoma XIAOHONG HOU1*, JIALIN CHEN2*, QIANG ZHANG1, YINCHUN FAN1, CHENGMING XIANG1, GUIYIN ZHOU1, FANG CAO1 and SHENGTAO YAO1 1Department of Cerebrovascular Disease, Affiliated Hospital of Zunyi Medical University;2 Department of Neonatology, The First People' s Hospital of Zunyi Affiliated to Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China Received October 15, 2019; Accepted October 6, 2020 DOI: 10.3892/etm.2020.9493 Abstract. Glioblastoma multiforme (GBM) is a common and immune genes of interest. The interaction network of malignant tumor type of the nervous system. The purpose immune‑regulatory genes constructed in the present study of the present study was to establish a regulatory network of enhances the current understanding of mechanisms associated immune‑associated genes affecting the prognosis of patients with poor prognosis of patients with GBM. The risk score with GBM. The GSE4290, GSE50161 and GSE2223 datasets model established in the present study may be used to evaluate from the Gene Expression Omnibus database were screened the prognosis of patients with GBM. to identify common differentially expressed genes (co‑DEGs). A functional enrichment analysis indicated that the co‑DEGs Introduction were mainly enriched in cell communication, regulation of enzyme activity, immune response, nervous system, cytokine Glioblastoma multiforme (GBM) is one of the most malig‑ signaling in immune system and the AKT signaling pathway. nant tumor types of the central nervous system, with short The co‑DEGs accumulated in immune response were then median survival and poor prognosis.
  • Anti-Müllerian Hormone in Stallions and Mares: Physiological Variations, Clinical Applications, and Molecular Aspects

    Anti-Müllerian Hormone in Stallions and Mares: Physiological Variations, Clinical Applications, and Molecular Aspects

    University of Kentucky UKnowledge Theses and Dissertations--Veterinary Science Veterinary Science 2014 ANTI-MÜLLERIAN HORMONE IN STALLIONS AND MARES: PHYSIOLOGICAL VARIATIONS, CLINICAL APPLICATIONS, AND MOLECULAR ASPECTS Anthony N.J. Claes University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Claes, Anthony N.J., "ANTI-MÜLLERIAN HORMONE IN STALLIONS AND MARES: PHYSIOLOGICAL VARIATIONS, CLINICAL APPLICATIONS, AND MOLECULAR ASPECTS" (2014). Theses and Dissertations-- Veterinary Science. 18. https://uknowledge.uky.edu/gluck_etds/18 This Doctoral Dissertation is brought to you for free and open access by the Veterinary Science at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Veterinary Science by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless an embargo applies.
  • Ncomms2254.Pdf

    Ncomms2254.Pdf

    ARTICLE Received 3 May 2012 | Accepted 5 Nov 2012 | Published 4 Dec 2012 DOI: 10.1038/ncomms2254 The RB family is required for the self-renewal and survival of human embryonic stem cells Jamie F. Conklin1,2,3, Julie Baker2,3 & Julien Sage1,2,3 The mechanisms ensuring the long-term self-renewal of human embryonic stem cells are still only partly understood, limiting their use in cellular therapies. Here we found that increased activity of the RB cell cycle inhibitor in human embryonic stem cells induces cell cycle arrest, differentiation and cell death. Conversely, inactivation of the entire RB family (RB, p107 and p130) in human embryonic stem cells triggers G2/M arrest and cell death through functional activation of the p53 pathway and the cell cycle inhibitor p21. Differences in E2F target gene activation upon loss of RB family function between human embryonic stem cells, mouse embryonic stem cells and human fibroblasts underscore key differences in the cell cycle regulatory networks of human embryonic stem cells. Finally, loss of RB family function pro- motes genomic instability in both human and mouse embryonic stem cells, uncoupling cell cycle defects from chromosomal instability. These experiments indicate that a homeostatic level of RB activity is essential for the self-renewal and the survival of human embryonic stem cells. 1 Department of Pediatrics, Stanford Medical School, Stanford, California 94305, USA. 2 Department of Genetics, Stanford Medical School, Stanford, California 94305, USA. 3 Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medical School, Stanford, California 94305, USA. Correspondence and requests for materials should be addressed to J.S.
  • Selective Estrogen Receptor Modulators: Discrimination of Agonistic Versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells

    Selective Estrogen Receptor Modulators: Discrimination of Agonistic Versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells

    [CANCER RESEARCH 64, 1522–1533, February 15, 2004] Selective Estrogen Receptor Modulators: Discrimination of Agonistic versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells Jonna Frasor,1 Fabio Stossi,1 Jeanne M. Danes,1 Barry Komm,2 C. Richard Lyttle,2 and Benita S. Katzenellenbogen1 1Department of Molecular and Integrative Physiology, University of Illinois and College of Medicine, Urbana, Illinois, and 2Women’s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania ABSTRACT tures in these women; however, some detrimental side effects such as an increased risk of endometrial cancer, stroke, and pulmonary embolism Selective estrogen receptor modulators (SERMs) such as tamoxifen are were also associated with tamoxifen treatment (7). Ral was examined in effective in the treatment of many estrogen receptor-positive breast cancers the Multiple Outcomes of Raloxifene Evaluation trial and found to be and have also proven to be effective in the prevention of breast cancer in women at high risk for the disease. The comparative abilities of tamoxifen effective in reducing the incidence of osteoporosis in postmenopausal versus raloxifene in breast cancer prevention are currently being compared in women, as well as the incidence of breast cancer but, unlike tamoxifen, the Study of Tamoxifen and Raloxifene trial. To better understand the actions without the increased risk of endometrial cancer (8, 9). On the basis of the of these compounds in breast cancer, we have examined their effects on the positive outcome of these trials, the Study of Tamoxifen and Raloxifene expression of ϳ12,000 genes, using Affymetrix GeneChip microarrays, with trial was begun in 1999 to directly compare the effects of these two quantitative PCR verification in many cases, categorizing their actions as SERMs, tamoxifen and Ral, in prevention of breast cancer (10, 11).
  • Observation and a Numerical Study of Gravity Waves During Tropical Cyclone Ivan (2008)

    Observation and a Numerical Study of Gravity Waves During Tropical Cyclone Ivan (2008)

    Open Access Atmos. Chem. Phys., 14, 641–658, 2014 Atmospheric www.atmos-chem-phys.net/14/641/2014/ doi:10.5194/acp-14-641-2014 Chemistry © Author(s) 2014. CC Attribution 3.0 License. and Physics Observation and a numerical study of gravity waves during tropical cyclone Ivan (2008) F. Chane Ming1, C. Ibrahim1, C. Barthe1, S. Jolivet2, P. Keckhut3, Y.-A. Liou4, and Y. Kuleshov5,6 1Université de la Réunion, Laboratoire de l’Atmosphère et des Cyclones, UMR8105, CNRS-Météo France-Université, La Réunion, France 2Singapore Delft Water Alliance, National University of Singapore, Singapore, Singapore 3Laboratoire Atmosphères, Milieux, Observations Spatiales, UMR8190, Institut Pierre-Simon Laplace, Université Versailles-Saint Quentin, Guyancourt, France 4Center for Space and Remote Sensing Research, National Central University, Chung-Li 3200, Taiwan 5National Climate Centre, Bureau of Meteorology, Melbourne, Australia 6School of Mathematical and Geospatial Sciences, Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Australia Correspondence to: F. Chane Ming ([email protected]) Received: 3 December 2012 – Published in Atmos. Chem. Phys. Discuss.: 24 April 2013 Revised: 21 November 2013 – Accepted: 2 December 2013 – Published: 22 January 2014 Abstract. Gravity waves (GWs) with horizontal wavelengths ber 1 vortex Rossby wave is suggested as a source of domi- of 32–2000 km are investigated during tropical cyclone (TC) nant inertia GW with horizontal wavelengths of 400–800 km, Ivan (2008) in the southwest Indian Ocean in the upper tropo- while shorter scale modes (100–200 km) located at northeast sphere (UT) and the lower stratosphere (LS) using observa- and southeast of the TC could be attributed to strong local- tional data sets, radiosonde and GPS radio occultation data, ized convection in spiral bands resulting from wave number 2 ECMWF analyses and simulations of the French numerical vortex Rossby waves.
  • Prospective Isolation of NKX2-1–Expressing Human Lung Progenitors Derived from Pluripotent Stem Cells

    Prospective Isolation of NKX2-1–Expressing Human Lung Progenitors Derived from Pluripotent Stem Cells

    The Journal of Clinical Investigation RESEARCH ARTICLE Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells Finn Hawkins,1,2 Philipp Kramer,3 Anjali Jacob,1,2 Ian Driver,4 Dylan C. Thomas,1 Katherine B. McCauley,1,2 Nicholas Skvir,1 Ana M. Crane,3 Anita A. Kurmann,1,5 Anthony N. Hollenberg,5 Sinead Nguyen,1 Brandon G. Wong,6 Ahmad S. Khalil,6,7 Sarah X.L. Huang,3,8 Susan Guttentag,9 Jason R. Rock,4 John M. Shannon,10 Brian R. Davis,3 and Darrell N. Kotton1,2 2 1Center for Regenerative Medicine, and The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. 3Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA. 4Department of Anatomy, UCSF, San Francisco, California, USA. 5Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. 6Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, Massachusetts, USA. 7Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. 8Columbia Center for Translational Immunology & Columbia Center for Human Development, Columbia University Medical Center, New York, New York, USA. 9Department of Pediatrics, Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee, USA. 10Division of Pulmonary Biology, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA. It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1–expressing (NKX2-1+) precursor cells.
  • Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells

    Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells

    Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897
  • Development of the Endochondral Skeleton

    Development of the Endochondral Skeleton

    Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Development of the Endochondral Skeleton Fanxin Long1,2 and David M. Ornitz2 1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 2Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110 Correspondence: fl[email protected] SUMMARY Much of the mammalian skeleton is composed of bones that originate from cartilage templates through endochondral ossification. Elucidating the mechanisms that control endochondral bone development is critical for understanding human skeletal diseases, injury response, and aging. Mouse genetic studies in the past 15 years have provided unprecedented insights about molecules regulating chondrocyte formation, chondrocyte maturation, and osteoblast differ- entiation, all key processes of endochondral bone development. These include the roles of the secreted proteins IHH, PTHrP, BMPs, WNTs, and FGFs, their receptors, and transcription factors such as SOX9, RUNX2, and OSX, in regulating chondrocyte and osteoblast biology. This review aims to integrate the known functions of extracellular signals and transcription factors that regulate development of the endochondral skeleton. Outline 1 Introduction 5 Osteoblastogenesis 2 Mesenchymal condensation 6 Closing remarks 3 Chondrocyte differentiation References 4 Growth plate development Editors: Patrick P.L. Tam, W. James Nelson, and Janet Rossant Additional Perspectives on Mammalian Development available at www.cshperspectives.org Copyright # 2013 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a008334 Cite this article as Cold Spring Harb Perspect Biol 2013;5:a008334 1 Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press F.
  • Character Set Migration Best Practices For

    Character Set Migration Best Practices For

    Character Set Migration Best Practices $Q2UDFOH:KLWH3DSHU October 2002 Server Globalization Technology Oracle Corporation Introduction - Database Character Set Migration Migrating from one database character set to another requires proper strategy and tools. This paper outlines the best practices for database character set migration that has been utilized on behalf of hundreds of customers successfully. Following these methods will help determine what strategies are best suited for your environment and will help minimize risk and downtime. This paper also highlights migration to Unicode. Many customers today are finding Unicode to be essential to supporting their global businesses. Oracle provides consulting services for very large or complex environments to help minimize the downtime while maximizing the safe migration of business critical data. Why migrate? Database character set migration often occurs from a requirement to support new languages. As companies internationalize their operations and expand services to customers all around the world, they find the need to support data storage of more World languages than are available within their existing database character set. Historically, many legacy systems required support for only one or possibly a few languages; therefore, the original character set chosen had a limited repertoire of characters that could be supported. For example, in America a 7-bit character set called ASCII is satisfactory for supporting English data exclusively. While in Europe a variety of 8 bit European character sets can support specific subsets of European languages together with English. In Asia, multi byte character sets that could support a given Asian language and English were chosen. These were reasonable choices that fulfilled the initial requirements and provided the best combination of economy and performance.
  • Material and Method

    Material and Method

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Spiral - Imperial College Digital Repository Attenuation of Hedgehog acyltransferase-catalyzed Sonic hedgehog palmitoylation causes reduced signaling, proliferation and invasiveness of human carcinoma cells Shu-Chun Chang 1, #, Antonio D Konitsiotis 1, Biljana Jovanović 1, *, Paulina Ciepla 2, 3, Naoko Masumoto 2, 3, Christopher P. Palmer 4, Edward W. Tate 2, 3, John R. Couchman 5 and Anthony I. Magee 1, 3 1 Molecular Medicine Section, National Heart & Lung Institute Imperial College London, Sir Alexander Fleming Building, South Kensington London SW7 2AZ, UK 2 Department of Chemistry, Imperial College London, South Kensington London SW7 2AZ, UK 3 Institute of Chemical Biology, Imperial College London 4 Institute for Health Research and Policy, London Metropolitan University London N7 8DB, UK 5 Department of Biomedical Sciences, University of Copenhagen, Biocenter, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark # Current address: Department of Biological Sciences, National University of Singapore 14 Science Drive 4, S1A-05-11, Singapore 117543 * Current address: Department of Biosciences and Nutrition, Karolinska Institutet SE-141 57 Huddinge, Sweden Running title: Carcinoma dependence on Hhat Key words: sonic hedgehog; Hedgehog acyltransferase; MBOAT; carcinoma; pancreatic; lung Corresponding author: Anthony I. Magee, Molecular Medicine Section, National Heart & Lung Institute Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Tel: +44 (0)20 7594 3135 E-mail: [email protected] Abbreviations: PDAC, pancreatic ductal adenocarcinoma; NSCLC, non-small cell lung cancer; Shh, Sonic hedgehog; Hhat, Hedgehog acyltransferase; KD, knockdown; siRNA, small interfering RNA; CFSE, 5(6)-Carboxyfluorescein diacetate N-succinimidyl ester; ALP, alkaline phosphatase 1 ABSTRACT Overexpression of Hedgehog family proteins contributes to the aetiology of many cancers.