DOCSLIB.ORG

Gene Regulatory Networks and Cell Lineages That Underlie The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Regulatory Networks and Cell Lineages That Underlie The PAPER Gene regulatory networks and cell lineages that COLLOQUIUM underlie the formation of skeletal muscle Margaret Buckinghama,1 aDepartment of Developmental and Stem Cell Biology, CNRS UMR 3738, Institut Pasteur, 75015 Paris, France Edited by Ellen V. Rothenberg, California Institute of Technology, Pasadena, CA, and accepted by Editorial Board Member Neil H. Shubin January 18, 2017 (received for review August 27, 2016) Skeletal muscle in vertebrates is formed by two major routes, as with emphasis on the formation of head muscles and lineage rela- illustrated by the mouse embryo. Somites give rise to myogenic tionships with the heart. The focus will be on amniote myogenesis, progenitors that form all of the muscles of the trunk and limbs. based on the mouse as a genetic model, with embryological back- The behavior of these cells and their entry into the myogenic ground provided by experimental manipulations in avians. program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck Skeletal Muscles of the Trunk and Limbs muscles do not derive from somites, but mainly form from meso- All of the skeletal muscles present in the trunk and limbs are derm in the pharyngeal region. Entry into the myogenic program derived from somites, segments of paraxial mesoderm that form also depends on the myogenic determination factor (MyoD) family progressively on either side of the body axis from the anterior to of genes, but Pax3 is not expressed in these myogenic progenitors, the posterior of the developing embryo (1). Muscles form after where different gene regulatory networks function, with T-box delamination of cells from the dorsal somite, the dermomyo- factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2)as tome, which maintains an epithelial structure after cells in the key upstream genes. The regulatory genes that underlie the for- ventral part of the somite have acquired a mesenchymal phe- mation of these muscles are also important players in cardiogen- notype, forming the sclerotome, which subsequently gives rise to esis, expressed in the second heart field, which is a major source of bone and cartilage of the vertebral column and ribs. At different myocardium and of the pharyngeal arch mesoderm that gives rise axial levels, myogenic progenitors from the part of the somite BIOLOGY to skeletal muscles. The demonstration that both types of striated adjacent to the axial structures of the neural tube and notochord DEVELOPMENTAL muscle derive from common progenitors comes from clonal anal- will form the epaxial myotome, which contributes to back mus- yses that have established a lineage tree for parts of the myocardium cles, while the hypaxial myotome gives rise to body wall muscles. and different head and neck muscles. Evolutionary conservation of At limb level, myogenic progenitors migrate out into the limb the two routes to skeletal muscle in vertebrates extends to chordates, bud and subsequently differentiate to form the muscles of the to trunk muscles in the cephlochordate Amphioxus andtomuscles limb. Cell migration from cervical somites is also important for derived from cardiopharyngeal mesoderm in the urochordate Ciona, the formation of the diaphragm muscle more anteriorly. As de- where a related gene regulatory network determines cardiac or skel- velopment proceeds, the initial muscle primordia, under the ’ etal muscle cell fates. In conclusion, Eric Davidson s visionary contri- action of surrounding connective tissue, become subdivided into bution to our understanding of gene regulatory networks and their distinct muscle masses; innervation takes place; and tendinous evolution is acknowledged. junctions with bones are established. In the initial waves of epaxial and hypaxial myogenesis, myogenic progenitors enter the skeletal myogenesis | muscle origins | second heart field | muscle program and differentiate into muscle. It is only later, gene regulatory networks | cell lineages when the epithelial structure of the central dermomyotome breaks down and cells enter the underlying muscle masses, that ovement is a fundamental requirement for animal survival, some of these cells do not differentiate, but constitute a reserve Mboth for finding food/feeding and for avoiding predators/ of myogenic progenitors for subsequent muscle growth and later locating to a propitious environment, and depends on cells with muscle regeneration. In the limbs, part of the population of contractile properties, mainly based on actomyosin motor activ- myogenic cells is also retained as a progenitor pool. ity. In more sophisticated organisms, specialized contractile pro- The gene regulatory network (2) that governs muscle pro- teins are present in muscle cells. In vertebrates, striated muscle genitor cell behavior (Fig. 1A) and controls activation of the permits movement and also underlies the pumping activity of the myogenic determination genes (Fig. 1B) is dominated by paired heart, which, like the simpler peristaltic pumps present in the box factor 3 gene (Pax3) (3), which is first expressed in pre- vascular system of many animals, performs a vital function in somitic mesoderm immediately anterior to the first somite and ensuring the circulation of nutrients within the body. Striated then throughout the early epithelial somite, before becoming muscles contain a range of distinct and overlapping contractile restricted to myogenic progenitors of the dermomyotome. protein isoforms, adapted to functional requirements of the motor Forkhead box protein factor c2 (Foxc2) is coexpressed with Pax3 activity of different skeletal muscles or of contractility in different in the early somite and then is expressed, together with Foxc1,at cardiac compartments of the heart. Although the contractile ap- paratus is similar at the protein level, the upstream regulation of cardiac or skeletal muscle genes is different. Skeletal muscle for- This paper results from the Arthur M. Sackler Colloquium of the National Academy of mation depends on myogenic regulatory factors of the myogenic Sciences, “Gene Regulatory Networks and Network Models in Development and Evolu- tion,” held April 12–14, 2016, at the Arnold and Mabel Beckman Center of the National determination factor (MyoD) family, whereas in cardiac muscle, Academies of Sciences and Engineering in Irvine, CA. The complete program and video these basic helix–loop–helix factors do not play a role, and other recordings of most presentations are available on the NAS website at www.nasonline.org/ families of transcription factors lead to the activation of striated Gene_Regulatory_Networks. muscle genes. The mesodermal progenitor cells that contribute to Author contributions: M.B. wrote the paper. cardiac and skeletal muscle also have distinct embryological origins, The author declares no conflict of interest. although it has now emerged that the skeletal muscles of the head This article is a PNAS Direct Submission. E.V.R. is a guest editor invited by the Editorial share common ancestry with the myocardium of the heart. In this Board. review, the formation of vertebrate skeletal muscle will be discussed, 1Email: [email protected]. www.pnas.org/cgi/doi/10.1073/pnas.1610605114 PNAS Early Edition | 1of8 Downloaded by guest on September 29, 2021 A myogenic progenitor cell B Sim2 survival and proliferation Pitx2 MyoD Msx1 myogenic limb Lbxl CXCR4 progenitor Pax3 Myf5 Meox2 Pax3 c-Met cell migration Dmrt2 Myf5 epaxial somite FgfR4 myogenesis versus Six1/4 MyoD hypaxial Foxc2 Sproutys cell renewal (Eya1/2) Myf5 somite/limb derm brown vascular endothelial and fat smooth muscle bone/cartilage Fig. 1. Gene regulatory networks at the onset of myogenesis in the trunk and limbs, where Pax3 plays a central role in controlling many aspects of myogenic progenitor cell behavior (A) including choice of the myogenic cell fate, survival, proliferation, migration, and entry into the differentiation program, which depends on activation of the myogenic determination genes at different sites where skeletal muscle formation is initiated in the mouse embryo (B). derm refers to the dorsal dermis. a high level in the sclerotome, where these Foxc transcription directly regulates enhancer sequences that govern most of the factors are required for the formation of bone and cartilage. spatiotemporal expression of this early myogenic determination Foxc2 remains expressed at a lower level in the dermomyotome, gene. The early epaxial enhancer that controls Myf5 expression in notably in the hypaxial domain. Genetic manipulations in the the epaxial somite does not depend directly on Pax3, but is acti- mouse embryo have shown that Pax3 and Foxc2 reciprocally vated by wingless-related integration site (WNT) signaling mole- inhibit each other (4). When the dose of Foxc2 is diminished, cules signaling from the neural tube and by doublesex- and mab- Pax3-dependent myogenic progenitors predominate, whereas related transcription factor 2 (Dmrt2), which is also implicated in diminution of the level of Pax3 favors nonmuscle cell fates, such maintaining somite integrity. Dmrt2 is a direct Pax3 target. Later as vascular smooth muscle or endothelial cells. Somitic cells are activation of MyoD is not directly dependent on Pax3, but depends maintained in a multipotent stem cell state, until the balance is on other factors acting at different sites of myogenesis, including tipped toward Pax3 or Foxc2. In this model, signaling from ad- the transcription factor encoded by the paired-like
Load more

Recommended publications
  • C.V. De Margaret Buckingham, Membre De L'académie Des Sciences
    Margaret Buckingham Élue Membre le 29 novembre 2005 dans la section Biologie intégrative Directeur de recherche au CNRS, Professeur à l'Institut Pasteur Œuvre scientifique Margaret Buckingham, de nationalités française et britannique, née en 1945, est diplômée (B.A., M.A., D. Phil.) de l’université d’Oxford. Depuis 1971, elle a mené sa carrière scientifique en France, d’abord dans le laboratoire de François Gros, puis à partir de 1987, en tant que chef de l’Unité de génétique moléculaire du développement, puis Professeur à l’Institut Pasteur où elle a été directrice du Département de biologie du développement. Elle est directeur de recherche au CNRS. Elle a présidé la section de Biologie du développement et de la reproduction au CNRS de 2001 à 2004 et la Société Française de Biologie du Développement de 2008 à 2011. Elle est actuellement membre du Comité Consultatif National d’Ethique (CCNE). Les recherches de Margaret Buckingham portent sur les mécanismes qui conduisent une cellule naïve à entrer dans un programme de différenciation tissulaire pendant le développement de l’organisme. Elle étudie les gènes qui régulent la formation et la régénération du muscle de squelette, ainsi que les populations cellulaires qui forment le cœur. Margaret Buckingham a effectué des études pionnières sur l’organisation des gènes du muscle et leurs différents modes d’expression pendant le développement. Parmi les gènes des facteurs de régulation myogénique, de la famille MyoD, l’expression de Myf5 précède la myogenèse chez l’embryon. En son absence, les cellules adoptent d’autres destins cellulaires, démontrant ainsi le rôle de Myf5 comme facteur de détermination myogénique.
    [Show full text]
  • Female Fellows of the Royal Society
    Female Fellows of the Royal Society Professor Jan Anderson FRS [1996] Professor Ruth Lynden-Bell FRS [2006] Professor Judith Armitage FRS [2013] Dr Mary Lyon FRS [1973] Professor Frances Ashcroft FMedSci FRS [1999] Professor Georgina Mace CBE FRS [2002] Professor Gillian Bates FMedSci FRS [2007] Professor Trudy Mackay FRS [2006] Professor Jean Beggs CBE FRS [1998] Professor Enid MacRobbie FRS [1991] Dame Jocelyn Bell Burnell DBE FRS [2003] Dr Philippa Marrack FMedSci FRS [1997] Dame Valerie Beral DBE FMedSci FRS [2006] Professor Dusa McDuff FRS [1994] Dr Mariann Bienz FMedSci FRS [2003] Professor Angela McLean FRS [2009] Professor Elizabeth Blackburn AC FRS [1992] Professor Anne Mills FMedSci FRS [2013] Professor Andrea Brand FMedSci FRS [2010] Professor Brenda Milner CC FRS [1979] Professor Eleanor Burbidge FRS [1964] Dr Anne O'Garra FMedSci FRS [2008] Professor Eleanor Campbell FRS [2010] Dame Bridget Ogilvie AC DBE FMedSci FRS [2003] Professor Doreen Cantrell FMedSci FRS [2011] Baroness Onora O'Neill * CBE FBA FMedSci FRS [2007] Professor Lorna Casselton CBE FRS [1999] Dame Linda Partridge DBE FMedSci FRS [1996] Professor Deborah Charlesworth FRS [2005] Dr Barbara Pearse FRS [1988] Professor Jennifer Clack FRS [2009] Professor Fiona Powrie FRS [2011] Professor Nicola Clayton FRS [2010] Professor Susan Rees FRS [2002] Professor Suzanne Cory AC FRS [1992] Professor Daniela Rhodes FRS [2007] Dame Kay Davies DBE FMedSci FRS [2003] Professor Elizabeth Robertson FRS [2003] Professor Caroline Dean OBE FRS [2004] Dame Carol Robinson DBE FMedSci
    [Show full text]
  • EMBO Conference Takes to the Sea Life Sciences in Portugal
    SUMMER 2013 ISSUE 24 encounters page 3 page 7 Life sciences in Portugal The limits of privacy page 8 EMBO Conference takes to the sea EDITORIAL Maria Leptin, Director of EMBO, INTERVIEW EMBO Associate Member Tom SPOTLIGHT Read about how the EMBO discusses the San Francisco Declaration Cech shares his views on science in Europe and Courses & Workshops Programme funds on Research Assessment and some of the describes some recent productive collisions. meetings for life scientists in Europe. concerns about Journal Impact Factors. PAGE 2 PAGE 5 PAGE 9 www.embo.org COMMENTARY INSIDE SCIENTIFIC PUBLISHING panels have to evaluate more than a hundred The San Francisco Declaration on applicants to establish a short list for in-depth assessment, they cannot be expected to form their views by reading the original publications Research Assessment of all of the applicants. I believe that the quality of the journal in More than 7000 scientists and 250 science organizations have by now put which research is published can, in principle, their names to a joint statement called the San Francisco Declaration on be used for assessment because it reflects how the expert community who is most competent Research Assessment (DORA; am.ascb.org/dora). The declaration calls to judge it views the science. There has always on the world’s scientific community to avoid misusing the Journal Impact been a prestige factor associated with the publi- Factor in evaluating research for funding, hiring, promotion, or institutional cation of papers in certain journals even before the impact factor existed. This prestige is in many effectiveness.
    [Show full text]
  • Margaret Buckingham, Discoveries in Skeletal and Cardiac Muscle Development, Elected to the National Academy of Science Michael a Rudnicki*
    Rudnicki Skeletal Muscle 2012, 2:12 http://www.skeletalmusclejournal.com/content/2/1/12 Skeletal Muscle COMMENT Open Access Margaret Buckingham, discoveries in skeletal and cardiac muscle development, elected to the National Academy of Science Michael A Rudnicki* Abstract Margaret Buckingham was presented as a newly elected member to the National Academy of Sciences on 28 April 2012. Over the course of her career, Dr Buckingham made many seminal contributions to the understanding of skeletal muscle and cardiac development. Her studies on cardiac progenitor populations has provided insight into understanding heart malformations, while her work on skeletal muscle progenitors has elucidated their embryonic origins and the transcriptional hierarchies controlling their developmental progression. Keywords: National Academy of Sciences, Cardiac development, Skeletal muscle development Commentary Her work on cardiac progenitor populations is of clinical Dr Margaret Buckingham, a much-respected investigator importance in understanding heart malformations. who has made many significant contributions to our Dr Buckingham has also made major contributions to understanding of skeletal muscle and cardiac develop- the molecular genetic analysis of skeletal muscle devel- ment, was elected to the National Academy of Sciences in opment. She was the first to analyze expression of the 2011 and presented on 28 April, 2012. Dr Buckingham is myogenic regulatory factors of the MyoD family during Professor in the Department of Developmental Biology at mouse embryogenesis [9] and the behavior of cells in the the Pasteur Institute in Paris. She has been awarded many absence of Myf5 [10]. prestigious distinctions including that of Officier de la Lé- Her more recent work demonstrated that skeletal gion d’Honneur and Officier de l'Ordre National du Mér- muscle growth depends on a somite-derived population of ite, to name but two.
    [Show full text]
  • PROGRAMME & Book of Abstracts
    PROGRAMME & book of abstracts “. MOVING FORWARD TOGETHER” www.EDBC2019Alicante.com ORGANISED BY CONTENTS SPONSORS & COLLABORATORS ORGANIZATION .......................................................................... 4 GENERAL INFORMATION ......................................................... 5 INSTRUCTIONS FOR SPEAKERS AND AUTHORS ................ 8 CONGRESS TIMETABLE ............................................................ 9 SCIENTIFIC PROGRAMME WEDNESDAY 23 .................................................................... 12 THURSDAY 24 ........................................................................ 13 FRIDAY 25 ............................................................................... 16 SATURDAY 26 ........................................................................ 19 POSTER SESSIONS ................................................................... 21 EXHIBITORS AND SPONSORS ................................................ 48 ABSTRACTS ................................................................................ 51 AUTHORS’ INDEX ...................................................................... 263 4 EDBC2019 EDBC2019 5 ORGANIZATION GENERAL INFORMATION ORGANIZING COMMITTEE INVITED SPEAKERS VENUE Ángela Nieto. Alicante Enrique Amaya. Manchester Auditorio de la Diputación de Alicante - ADDA Víctor Borrell. Alicante Detlev Arendt. Heidelberg Paseo Campoamor, s/n Sergio Casas-Tintó. Madrid Laure Bally Cuif. Paris 03010 Alicante, Spain Pilar Cubas. Madrid Fernando Casares. Sevilla www.addaalicante.es
    [Show full text]
  • Cardiac Cell Lineages That Form the Heart
    This is a free sample of content from The Biology of Heart Disease. Click here for more information on how to buy the book. Cardiac Cell Lineages that Form the Heart Sigole` ne M. Meilhac1, Fabienne Lescroart2,Ce´ dric Blanpain2,3, and Margaret E. Buckingham1 1Institut Pasteur, Department of Developmental and Stem Cell Biology, CNRS URA2578, 75015 Paris, France 2Universite´ Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium 3WELBIO, Universite´ Libre de Bruxelles, Brussels B-1070, Belgium Correspondence: [email protected]; [email protected] Myocardial cells ensure the contractility of the heart, which also depends on other meso- dermal cell types for its function. Embryological experiments had identified the sources of cardiac precursorcells. With the advent of genetic engineering, novel tools have been used to reconstruct the lineage tree of cardiac cells that contribute to different parts of the heart, map the development of cardiac regions, and characterize their genetic signature. Such knowl- edge is of fundamental importance for our understanding of cardiogenesis and also for the diagnosis and treatment of heart malformations. he sources of cells that form the different tracing experiments based on the engineered Tparts of the heart and their relationships to temporal and spatial expression of a reporter each other are of major fundamental interest gene in different cardiac progenitors and their for understanding cardiogenesis. They are also descendants, with the mouse as the principal of biomedical significance in the context of model system. congenital heart malformations and for future therapeutic approaches to cardiac malfunction SOURCES OF CARDIAC CELLS IN THE based on stem cell therapies.
    [Show full text]
  • Smutty Alchemy
    University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2021-01-18 Smutty Alchemy Smith, Mallory E. Land Smith, M. E. L. (2021). Smutty Alchemy (Unpublished doctoral thesis). University of Calgary, Calgary, AB. http://hdl.handle.net/1880/113019 doctoral thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY Smutty Alchemy by Mallory E. Land Smith A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN ENGLISH CALGARY, ALBERTA JANUARY, 2021 © Mallory E. Land Smith 2021 MELS ii Abstract Sina Queyras, in the essay “Lyric Conceptualism: A Manifesto in Progress,” describes the Lyric Conceptualist as a poet capable of recognizing the effects of disparate movements and employing a variety of lyric, conceptual, and language poetry techniques to continue to innovate in poetry without dismissing the work of other schools of poetic thought. Queyras sees the lyric conceptualist as an artistic curator who collects, modifies, selects, synthesizes, and adapts, to create verse that is both conceptual and accessible, using relevant materials and techniques from the past and present. This dissertation responds to Queyras’s idea with a collection of original poems in the lyric conceptualist mode, supported by a critical exegesis of that work.
    [Show full text]
  • Muscle Coding Sequences and Their Regulation During Myogenesis : Cloning of Muscle Actin Cdna Probes A
    Muscle coding sequences and their regulation during myogenesis : cloning of muscle actin cDNA probes A. Minty, M. Caravatti, B. Robert, Arlette Cohen, P. Daubas, A. Weydert, F. Gros, Margaret Buckingham To cite this version: A. Minty, M. Caravatti, B. Robert, Arlette Cohen, P. Daubas, et al.. Muscle coding sequences and their regulation during myogenesis : cloning of muscle actin cDNA probes. Reproduction Nutrition Développement, 1981, 21 (2), pp.247-255. hal-00897814 HAL Id: hal-00897814 https://hal.archives-ouvertes.fr/hal-00897814 Submitted on 1 Jan 1981 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. Muscle coding sequences and their regulation during myogenesis : cloning of muscle actin cDNA probes A. MINTY M. CARAVATTI, B. ROBERT, Arlette COHEN P. DAUBAS A. WEY- DERT F. GROS Margaret BUCKINGHAM Département de Biologie moléculaire, Institut Pasteur 25, rue du Dr. Roux, 75724 Paris Cedex. Summary. For a number of years our group has been mainly interested in the regulation of muscle gene expression during myogenesis. Using primary cultures and cell lines we have tried to find out whether the coding sequences for muscle proteins are already present in an unexpressed form or if there is a transcriptional switch at the onset of differentiation.
    [Show full text]
  • Directory 2016/17 the Royal Society of Edinburgh
    cover_cover2013 19/04/2016 16:52 Page 1 The Royal Society of Edinburgh T h e R o Directory 2016/17 y a l S o c i e t y o f E d i n b u r g h D i r e c t o r y 2 0 1 6 / 1 7 Printed in Great Britain by Henry Ling Limited, Dorchester, DT1 1HD ISSN 1476-4334 THE ROYAL SOCIETY OF EDINBURGH DIRECTORY 2016/2017 PUBLISHED BY THE RSE SCOTLAND FOUNDATION ISSN 1476-4334 The Royal Society of Edinburgh 22-26 George Street Edinburgh EH2 2PQ Telephone : 0131 240 5000 Fax : 0131 240 5024 email: [email protected] web: www.royalsoced.org.uk Scottish Charity No. SC 000470 Printed in Great Britain by Henry Ling Limited CONTENTS THE ORIGINS AND DEVELOPMENT OF THE ROYAL SOCIETY OF EDINBURGH .....................................................3 COUNCIL OF THE SOCIETY ..............................................................5 EXECUTIVE COMMITTEE ..................................................................6 THE RSE SCOTLAND FOUNDATION ..................................................7 THE RSE SCOTLAND SCIO ................................................................8 RSE STAFF ........................................................................................9 LAWS OF THE SOCIETY (revised October 2014) ..............................13 STANDING COMMITTEES OF COUNCIL ..........................................27 SECTIONAL COMMITTEES AND THE ELECTORAL PROCESS ............37 DEATHS REPORTED 26 March 2014 - 06 April 2016 .....................................................43 FELLOWS ELECTED March 2015 ...................................................................................45
    [Show full text]
  • Muscle Satellite Cells Are Primed for Myogenesis but Maintain Quiescence with Sequestration of Myf5 Mrna Targeted by Microrna-31 in Mrnp Granules
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Cell Stem Cell Short Article Muscle Satellite Cells Are Primed for Myogenesis but Maintain Quiescence with Sequestration of Myf5 mRNA Targeted by microRNA-31 in mRNP Granules Colin G. Crist,1,2 Didier Montarras,1 and Margaret Buckingham1,* 1CNRS URA 2578, Department of Developmental Biology, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France 2Present address: Lady Davis Institute for Medical Research and Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada *Correspondence: [email protected] http://dx.doi.org/10.1016/j.stem.2012.03.011 SUMMARY Pax3 in many muscles (Relaix et al., 2006); however, unlike their embryonic counterparts, more than 95% have already activated Regeneration of adult tissues depends on stem cells the Myf5 gene in the course of their history (Kuang et al., 2007), that are primed to enter a differentiation program, indicating that they had entered the myogenic program. Further- while remaining quiescent. How these two character- more, the majority of quiescent satellite cells maintain Myf5 tran- istics can be reconciled is exemplified by skeletal scription (Beauchamp et al., 2000; Pallafacchina et al., 2010). muscle in which the majority of quiescent satellite Here, we examine the posttranscriptional mechanisms that cells transcribe the myogenic determination gene function to repress the translation of Myf5 mRNA, thereby holding quiescent satellite cells poised to enter the myogenic Myf5, without activating the myogenic program. We program. show that Myf5 mRNA, together with microRNA-31, which regulates its translation, is sequestered in RESULTS mRNP granules present in the quiescent satellite cell.
    [Show full text]
  • IX Meeting of the Spanish Society for Developmental Biology November 12-14, 2012 Granada
    IX Meeting of the Spanish Society for Developmental Biology November 12-14, 2012 Granada Abstract Book Index 01- Programme .................................................................................................................................................. 0 8 02- Principal Lectures .................................................................................................................................... 13 1 -Opening lecture Eric Olson .................................................................................................................................... 14 03- Invited Speakers ........................................................................................................................................ 15 Session 1 – Developmental Genomics................................................................................................. 16 1- Jose Luis Gómez Skarmeta (CABD, Sevilla) ......................................................................................................... 17 Session 2 – Tissue Patterning and Differentiation ......................................................................... 18 1- Anton Moorman (AMC, Amsterdam, Netherlands) ................................................................................................ 19 2 - Mar Ruiz (CBMSO, Madrid) ................................................................................................................................... 20 Session 3 – Cell Adhesion and Migration ..........................................................................................
    [Show full text]
  • Transcriptome Analyses Based on Genetic Screens
    Lagha et al. BMC Genomics 2010, 11:696 http://www.biomedcentral.com/1471-2164/11/696 RESEARCH ARTICLE Open Access Transcriptome analyses based on genetic screens for Pax3 myogenic targets in the mouse embryo Mounia Lagha6†, Takahiko Sato6†, Béatrice Regnault1, Ana Cumano2, Aimée Zuniga3, Jonathan Licht4, Frédéric Relaix5, Margaret Buckingham6* Abstract Background: Pax3 is a key upstream regulator of the onset of myogenesis, controlling progenitor cell survival and behaviour as well as entry into the myogenic programme. It functions in the dermomyotome of the somite from which skeletal muscle derives and in progenitor cell populations that migrate from the somite such as those of the limbs. Few Pax3 target genes have been identified. Identifying genes that lie genetically downstream of Pax3 is therefore an important endeavour in elucidating the myogenic gene regulatory network. Results: We have undertaken a screen in the mouse embryo which employs a Pax3GFP allele that permits isolation of Pax3 expressing cells by flow cytometry and a Pax3PAX3-FKHR allele that encodes PAX3-FKHR in which the DNA binding domain of Pax3 is fused to the strong transcriptional activation domain of FKHR. This constitutes a gain of function allele that rescues the Pax3 mutant phenotype. Microarray comparisons were carried out between Pax3GFP/ + and Pax3GFP/PAX3-FKHR preparations from the hypaxial dermomyotome of somites at E9.5 and forelimb buds at E10.5. A further transcriptome comparison between Pax3-GFP positive and negative cells identified sequences specific to myogenic progenitors in the forelimb buds. Potential Pax3 targets, based on changes in transcript levels on the gain of function genetic background, were validated by analysis on loss or partial loss of function Pax3 mutant backgrounds.
    [Show full text]