DOCSLIB.ORG

Proquest Dissertations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Proquest Dissertations The Expression and Regulation of the Po Gene During Development of the Rat: Regulation of Basal Level and Early Expression by Meng-Jen Lee Department of Anatomy and Developmental Biology University College London A thesis presented for the degree of Doctor of Philosophy The University of London, 1998 ProQuest Number: U642130 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642130 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Acknowledgements I wish to thank Professors Kristjan lessen and Rhona Mirsky for their guidance and enthusiasm throught the course of this work. I also thank Dr. Myrna Dent and Dr. Eric Parmantier for their help and numerous discussions, especially in in situ hybridization technique. I am grateful to Dr. Angela Brennan who contributed to the set up of the neural crest cultures and the study of the regulation of Po protein, and Dr. Ester Calle for contributing to the study of the lineage segregation. I thank Dr Louise Morgan, Dr Helen Stewart and Dr. Ziping Dong for their discussion and help, especially in the early days. I also acknowledge Charlotte Dean, Christiane Zoidl and Mary Rahman for technical support and making working in the lab easy. I am grateful to Dr. V. Pachnis, Dr. D. Ish-Horowilz, Dr. C. Birchmeier, Dr. C. Dickson, Dr. Wilkinson, Dr. G. Lemke, Dr. I. Griffth, Dr. J. Lewis, Dr. D. Henrique for their gift of plasmids, Dr. B. Zalc for the PLP transgenic mice. I want to thank Dr. Jon Clark and Dr. Paul Martin for the micrscope and photography setup. Dr. Sue Manning for sharing her methods, Steve Harsum and C P Ma for their advice on computer methods. Finally I thank my parents and my family for their support over many years. TABLE OF CONTENTS TITLE 1 ACKNOWLEDGEMENTS 2 TABLE OF CONTENTS 3 ABSTRACT 5 LIST OF TABLES AND ILLUSTRATIVE MATERIAL 7 ABBREVIATIONS 9 CHAPTER 1 : GENERAL INTRODUCTION 11 1.0 Table of contents 12 1.1 PNS glia 15 1.2 The molecular phenotypes of Schwann cells 18 1.3 Neuronal influence on Schwann cells 31 1.4 Wallerian degeneration 34 1.5 Myelination and the structure of myelinated fibres 36 1.6 Other Schwann cell functions 37 1.7 The Po molecule 37 1.8 The neural crest 42 1.9 Gliogenesis and neurogenesis during the formation of the dorsal root ganglion 53 1.10 Axon/Schwann cell interactions during the formation of nerves 55 1.11 The Schwann cell precursor 56 1.12 The CNS/PNS transitional zone 58 1.13 The gut 59 1.14 The placode 61 1.15 The ear 65 1.16 The nose 75 1.17 Illustrative material 81 CHAPTER 2: Materials and Methods 87 CHAPTER 3: The differential regulation of Po gene in the 2 mature phenotypes of the Schwann cell lineage 110 3.0 Table of contents 111 3.1 Introduction 112 3.2 Results 3.3 Discussion 119 3.4 Ilustrative material 121 CHAPTER 4: The study of Po gene expression in the migrating neural crest and its derivatives 126 4.0 Table of contents 127 4.1 Introduction 129 4.2 Results 135 4.3 Discussion 145 4.4 Illustrative material 158 CHAPTER 5: The study of Po gene expression in the development of the inner ear 168 5.0 Table of contents 169 5.1 Introduction 171 5.2 Results 175 5.3 Discussion 180 5.4 Ilustrative material 196 CHAPTER 6: General Discussion 201 CHAPTER 7 : References 208 Abstract This thesis represents a study of the Po gene, the major myelin protein gene in Schwann cells, during development of the rat. The major function of Po is in compaction of the myelin membrane during myelination, but I have found, using sensitive in situ hybridisation methods, that the gene is expressed much earlier than the onset of myelination. My experiments show that the Po gene is constitutively expressed early in development of the Schwann cell lineage, and that in adult nerves the Po gene is up-regulated and down-regulated differently in the two mature Schwann cell phenotypes. I found that Po mRNA is expressed at similar levels in Schwann cells at embryonic day 18, both in the sciatic nerve, where many Schwann cells will begin to myelinate shortly after birth, and also in the sympathetic trunk, where most Schwann cells are non-myelinating. Exploration of Po expression at earlier developmental stages, revealed that Po mRNA is expressed in Schwann cell precursors, the immediate precursors of Schwann cells in peripheral nerves, and also in a subpopulation of neural crest cells. I used the neural crest/ peripheral nervous system lineage, a relative simple model, to understand how cells of the neural lineage differentiated after they were generated from ectodermal cells in the process of neurulation. In the second part of my study, by correlating Po mRNA expression patterns in whole mount preparations and sections at embryonic ages from day 10 to day 14 with known neural crest migration patterns and with expression of neuronal and other neural crest lineage markers, I conclude that Po expression is restricted to a subpopulation of migrating crest cells which are likely to represent a cell population showing early commitment to the glial lineage. Special attention is paid to expression patterns in the forelimb and hind limb regions at embryo day 12, to expression patterns in the head at embryonic days 10 and 11, and to expression patterns in the developing gut at embryonic days 12-14. The onset of Po mRNA expression is compared with that of other molecules known to be specific to the Schwann cell lineage, and it is concluded that Po is the earliest well characterised marker of a glial phenotype. In the third part of the study I describe the unexpected expression of Po mRNA in the inner ear, where it has not previously been described. The expression of Po in the otic placode/pit stage at embryonic day 10, in the otic vesicle at embryonic day 12 and in the embryonic inner ear at later stages of development is described, and compared to several known molecular markers of the development of inner ear. The pattern of Po expression is broad but specific, with boundaries that clearly delineate segments of inner ear. Olfactory glial cells, which are placode derived, are Po positive during development. Po expression in olfactory glial cells persist through adulthood, although the olfactory nerves are not myelinated. List of Tables Table 1-1 Neural crest derivatives 43 Table 1-2 Derivatives of neural crest and placodes, categorised by cell type 63 Table 1-3 Contribution to the cranial ganglia by placodes and crest 63 Table 1-4 Combinatory code of transcription factors in placodes 65 Table 2-1 Restriction sites and polymerase used to generate riboprobes 109 Table 5-1 Comparison of neural crest and neurogenic placode 183 Table 5-2 The earliest innervation of inner ear 190 List of Illustrative Materials Figure 1-1 Molecular structure of Po protein 81 Figure 1-2 Diagrammatic representation of Po orientation in the myelin membrane 82 Figure 1-3 Neural crest migrating pathway in the trunk 83 Figure 1-4 Gross structure of inner ear 84 Figure 1-5 Structure of cochlea and Organ of Corti 85 Figure 1-6 recycling cells 86 Figure2-1 cDNA encoding the entire Po coding sequence 108 Figure3-1 Po mRNA in the neural crest and in developing sciatic nerves 121 Figure3-2 Axon-dependent and reversible down-regulation of Po mRNA in adult non-myelin-forming Schwann cells 123 Figure3-3 Removal of Schwann cells from axons leads to a fall in myelin related Po expression, while basal levels are relatively unaffected 124 Figure3-4 Schematic representation of Po mRNA distribution in cells of the Schwann cell lineage 125 Figure 4-1 RT-PCR of Po in developing embryo 158 Figure 4-2 Po expression in ElO 160 Figure 4-3 Po expression in El 1 ; comparison to TUJ-1 160 Figure 4-4 Po expression in E l2; comparison to TUJ-1, ErbB3 and Krox-20 160 Figure 4-5 Po expression in E l4 161 Figure 4-6 Developing enteric nervous system 162 Figure 4-7 Neural crest culture 164 Figure 4-8 The periodic pattern of Po expression in the migrating neural crest 165 Figure 4-9 A summary of Po expression during the generation of peripheral glial phenotypes 167 Figure 5-1 Po expression in El 1; comparison to Delta-1 194 Figures-2 Po expression in otic vesicle; comparison to PLP/DM-20 194 Figure 5-3 Po expression in E14 inner ear, serial sections 195 Figure 5-4 Po expression in utricle/cochlea/ganglion at E l4 196 Figure 5-5 Po compared to c-ret and BMP-4 in E l4 inner ear 197 Figure 5-6 Po compared to BMP-4 and serrate-1 in E l4 cochlea 199 Figure 5-7 Po compared to c-ret in E l4 utricle and cochlear 199 Figure 5-8 Po expression in developing olfactory nerves 200 ABBREVIATIONS 3’ UTR 3’ untranslated region ADS antibody diluting solution BDH dopamine-p-hydroxylase BMP-4 bone morphogenetic protein cAMP cyclic AMP CNPase 2’,3’,-cyclic nucleotide 3’-phosphodiesterase CNS central nervous system CNTF ciliary neurotrophic factor CSX cervical sympathetic trunk DMEM Dulbecco’s modified Eagle medium DREZ dorsal root entry zone DRG dorsal root ganglia E() embryonic day ENS enteric nervous system Gal-C galactocerebroside GAP-43 growth associated protein 43 GDNF glial cell line derived neurotrophic factor
Load more

Recommended publications
  • Sox9 Is Required for Invagination of the Otic Placode in Mice ⁎ Francisco Barrionuevo A, , Angela Naumann B, Stefan Bagheri-Fam A,1, Volker Speth C, Makoto M
    Available online at www.sciencedirect.com Developmental Biology 317 (2008) 213–224 www.elsevier.com/developmentalbiology Sox9 is required for invagination of the otic placode in mice ⁎ Francisco Barrionuevo a, , Angela Naumann b, Stefan Bagheri-Fam a,1, Volker Speth c, Makoto M. Taketo d, Gerd Scherer a, Annette Neubüser b a Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany b Developmental Biology, Institute of Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany c Cell Biology, Institute of Biology II, University of Freiburg, Schänzlestrasse 1, D-79104 Freiburg, Germany d Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan Received for publication 20 December 2007; revised 7 February 2008; accepted 8 February 2008 Available online 21 February 2008 Abstract The HMG-domain-containing transcription factor Sox9 is an important regulator of chondrogenesis, testis formation and development of several other organs. Sox9 is expressed in the otic placodes, the primordia of the inner ear, and studies in Xenopus have provided evidence that Sox9 is required for otic specification. Here we report novel and different functions of Sox9 during mouse inner ear development. We show that in mice with a Foxg1Cre-mediated conditional inactivation of Sox9 in the otic ectoderm, otic placodes form and express markers of otic specification. However, mutant placodes do not attach to the neural tube, fail to invaginate, and subsequently degenerate by apoptosis, resulting in a complete loss of otic structures. Transmission-electron microscopic analysis suggests that cell–cell contacts in the Sox9 mutant placodes are abnormal, although E-cadherin, N-cadherin, and beta-catenin protein expression are unchanged.
    [Show full text]
  • And Krox-20 and on Morphological Segmentation in the Hindbrain of Mouse Embryos
    The EMBO Journal vol.10 no.10 pp.2985-2995, 1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos G.M.Morriss-Kay, P.Murphy1,2, R.E.Hill1 and in embryos are unknown, but in human embryonal D.R.Davidson' carcinoma cells they include the nine genes of the Hox-2 cluster (Simeone et al., 1990). Department of Human Anatomy, South Parks Road, Oxford OXI 3QX The hindbrain and the neural crest cells derived from it and 'MRC Human Genetics Unit, Western General Hospital, Crewe are of particular interest in relation to the developmental Road, Edinburgh EH4 2XU, UK functions of RA because they are abnormal in rodent 2Present address: Istituto di Istologia ed Embriologia Generale, embryos exposed to a retinoid excess during or shortly before Universita di Roma 'la Sapienza', Via A.Scarpa 14, 00161 Roma, early neurulation stages of development (Morriss, 1972; Italy Morriss and Thorogood, 1978; Webster et al., 1986). Communicated by P.Chambon Human infants exposed to a retinoid excess in utero at early developmental stages likewise show abnormalities of the Mouse embryos were exposed to maternally administered brain and of structures to which cranial neural crest cells RA on day 8.0 or day 73/4 of development, i.e. at or just contribute (Lammer et al., 1985). Retinoid-induced before the differentiation of the cranial neural plate, and abnormalities of hindbrain morphology in rodent embryos before the start of segmentation. On day 9.0, the RA- include shortening of the preotic region in relation to other treated embryos had a shorter preotic hindbrain than the head structures, so that the otocyst lies level with the first controls and clear rhombomeric segmentation was pharyngeal arch instead of the second (Morriss, 1972; absent.
    [Show full text]
  • 20. Placodes and Sensory Development
    PLACODES AND 20. SENSORY DEVELOPMENT Letty Moss-Salentijn DDS, PhD Dr. Edwin S. Robinson Professor of Dentistry (in Anatomy and Cell Biology) E-mail: [email protected] READING ASSIGNMENT: Larsen 3rd Edition Chapter 12, Part 2. pp.379-389; Part 3. pp.390- 396; Chapter 13, pp.430-432 SUMMARY A series of ectodermal thickenings or placodes develop in the cephalic region at the periphery of the neural plate. Placodes are central to the development of the cranial sensory systems in vertebrates and are among the innovations that appeared in the early evolution of vertebrates. There are placodes for the three organs of special sense: olfactory, optic (lens) and otic placodes, and (epibranchial) placodes that give rise to the distal cells of the sensory ganglia of cranial nerves V, VII, IX and X. Placodes (with the possible exception of the olfactory placodes) form under the influence of surrounding cranial tissues. They do not appear to require the presence of neural crest. The mesoderm in the prechordal plate plays a significant role in the initial development of the placodes for the organs of special sense, while the pharyngeal pouch endoderm plays that role in the development of the epibranchial placodes. The development of the organs of special sense is described briefly. LEARNING OBJECTIVES You should be able to: a. Give a definition of placodes and describe their evolutionary significance. b. Name the different types of placodes, their locations in the developing embryo and their developmental fates. c. Discuss the early development of the placodes and some of the possible factors that feature in their development.
    [Show full text]
  • Otic Capsule Or Bony Labyrinth
    DEVELOPMENT OF EAR BY DR NOMAN ULLAH WAZIR DEVELOPMENT OF EAR The ears are composed of three anatomic parts: External ear: • Consisting of the auricle , external acoustic meatus, and the external layer of the tympanic membrane. Middle ear: • The internal layer of the tympanic membrane, and three small auditory ossicles, which are connected to the oval windowsof the internal ear. • Internal ear: Consisting of the vestibulocochlear organ, which is concerned with hearing and balance. • The external and middle parts of the ears are concerned with the transference of sound waves to the internal ears, which convert the waves into nerve impulses and registers changes in equilibrium. DEVELOPMENT OF INTERNALEAR The internal ears are the first to develop. • Otic placode: Early in the 4th week, a thickening of surface ectoderm takes place on each side of the myelencephalon,the caudal part of thehindbrain. • Inductive signals from the paraxial mesoderm and notochord stimulate the surface ectoderm to form theplacodes. • Each otic placode soon invaginates and sinks deep to the surface ectoderm into the underlying mesenchyme. • In so doing, it forms an otic pit. • The edges of the pit come together and fuse to forman otic vesicle the primordium of the membranous labyrinth. • The otic vesicle soon loses its connection with the surface ectoderm. • A diverticulum (endolymohatic appendage) grows from the vesicle and elongates to form the endolymphatic duct and sac. the rest of the oticvesicle differentiates into an expanded pars superior (Ventral saccularparts, which give rise to the sacculeand cochlearducts) and an initially tapered pars inferior (Dorsal utricular parts, from which thesmall endolymphaticducts, utricles and semicircular ductsarise).
    [Show full text]
  • Olfactory Epithelium: Development of the Nose Olfactory Epithelium: Development of the Nose
    DEVELOPMENT OF THE HEAD AND NECK PlacodesPlacodes andand thethe developmentdevelopment ofof organsorgans ofof specialspecial sensesense LL.. MMoossss--SaSalelentijnntijn Innovations in the early evolution of vertebrates ! DDeevveellooppmmeenntt ooff oorrggaannss ooff ssppeecciiaall sseennssee ((ppllaaccooddeess)) ! DDeevveellooppmmeenntt ooff aa llaarrggee nneeuurraall cciirrccuuiittrryy ((tthhee bbrraaiinn)) ttoo iinntteeggrraattee iinnppuutt aanndd rreessppoonnsseess ! DDeevveellooppmmeenntt ooff aann eeffffeeccttiivvee ffeeeeddiinngg aappppaarraattuuss (jaws)(jaws) ! DDeevveellooppmmeenntt ooff aann iimmpprroovveedd rreessppiirraattoorryy aappppaarraattuuss ((ggiillllss)) PLACODES Localized thickened areas of specialized ectoderm, lateral to the neural crest, at the border between neural plate and the future epidermis Brugmann SA, Moody SA (2005) Brugmann SA, Moody SA (2005) NEURAL PLATE NEURAL GROOVE Example: otic placode. Different kinds of placodes ! CCoonnttrriibbuuttiinngg ttoo oorrggaannss ooff ssppeecciiaall sseennssee:: "OlfactoryOlfactory "LensLens (only(only placodeplacode thatthat doesdoes notnot havehave neuralneural fate)fate) "OticOtic ! ContributingContributing toto distaldistal gangliaganglia ofof branchiomericbranchiomeric nneerrvveess:: "TrigeminalTrigeminal (Ophthalmic,V1)(Ophthalmic,V1) "EpibranchialEpibranchial (4)(4) ! Hypobranchial (2) (contribute to hypobranchial ganglia - frog only; not in chick, mouse, zebrafish) Distribution of placodes at 3 developmental stages A. Initial induction of placodes in pre-placodal
    [Show full text]
  • For Proteoglycans in Neurulation
    J. Anat. (1982), 134, 3, pp. 491-506 491 With 16figures Printed in Great Britain Culture of rat embryos with p-D-xyloside: evidence of a role for proteoglycans in neurulation GILLIAN M. MORRISS-KAY AND BETH CRUTCH Department ofHuman Anatomy, University of Oxford (Accepted 1 May 1981) INTRODUCTION The synthesis of sulphated glycosaminoglycans by early post-implantation rat embryos occurs at very low levels until the onset of neurulation, at which time there is an increase in the level ofsynthesis (as indicated by [3H]glucosamine incorporation) of chondroitin/chondroitin sulphate and heparan sulphate (Solursh & Morriss, 1977). In embryos undergoing neurulation, histochemical staining techniques have indicated that these sulphated glycosaminoglycans are localised in the ectodermal basement membrane and in the extracellular matrix and cell surface-associated material of the mesenchyme. The staining intensity is higher in the neural fold region than elsewhere in the embryo. They are probably present in the form of proteoglycan in association with hyaluronate (Morriss & Solursh, 1978a). In order to investigate further these stage and position-related histochemical differences, we have cultured rat embryos in vitro during neurulation and early somitogenesis in the presence of the xylose-derivative, /8-D-xyloside. This substance has been shown to bring about a reduction in the level of synthesis of protein-bound chondroitin sulphate and an increase in free chondroitin sulphate chains in both chondrogenic and non-chondrogenic systems (Schwartz, Ho & Dorfman, 1976; Galligani, Hopwood, Schwartz & Dorfman, 1975). Its activity is due to interference with the sequence of normal chondroitin sulphate-proteoglycan synthesis, as fol- lows. Prior to chondroitin sulphate chain synthesis, three sugar molecules, xylose and two galactose molecules, are added sequentially to certain serines of the core protein (for review, see Roden & Schwartz, 1975).
    [Show full text]
  • Fgfr1 Regulates Patterning of the Pharyngeal Region
    Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Fgfr1 regulates patterning of the pharyngeal region Nina Trokovic, Ras Trokovic, Petra Mai, and Juha Partanen1 Institute of Biotechnology, Viikki Biocenter, 00014-University of Helsinki, Finland Development of the pharyngeal region depends on the interaction and integration of different cell populations, including surface ectoderm, foregut endoderm, paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of Fgfr1 have craniofacial defects, some of which appeared to result from a failure in the early development of the second branchial arch. A stream of neural crest cells was found to originate from the rhombomere 4 region and migrate toward the second branchial arch in the mutants. Neural crest cells mostly failed to enter the second arch, however, but accumulated in a region proximal to it. Both rescue of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele specifically in neural crest cells indicated that Fgfr1 regulates the entry of neural crest cells into the second branchial arch non-cell- autonomously. Gene expression in the pharyngeal ectoderm overlying the developing second branchial arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration. [Keywords: Craniofacial development; fibroblast growth factor; branchial arch; hindbrain; neural crest; cell migration; cleft palate; Cre recombinase] Supplemental material is available at http://www.genesdev.org. Received October 1, 2002; revised version accepted October 17, 2002. Branchial arches of vertebrate embryos are transient (Lumsden and Krumlauf 1996; Rijli et al.
    [Show full text]
  • Second Order Division in Sectors As a Prepattern for Sensory Organs in Vertebrate Development Vincent Fleury, Alexis Peaucelle, Anick Abourachid, Olivia Plateau
    Second order division in sectors as a prepattern for sensory organs in vertebrate development Vincent Fleury, Alexis Peaucelle, Anick Abourachid, Olivia Plateau To cite this version: Vincent Fleury, Alexis Peaucelle, Anick Abourachid, Olivia Plateau. Second order division in sectors as a prepattern for sensory organs in vertebrate development. 2021. hal-03098723 HAL Id: hal-03098723 https://hal.archives-ouvertes.fr/hal-03098723 Preprint submitted on 5 Jan 2021 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. 1 Second order division in sectors as a prepattern for sensory organs in vertebrate development Vincent Fleury1, Alexis Peaucelle2, Anick Abourachid3 and Olivia Plateau1,3,4 1Laboratoire Matière et Systèmes Complexes, UMR 7057 Université de Paris/CNRS, 10 rue Alice Domont et Léonie Duquet, 75013 Paris, France. 2Institut Jean-Pierre Bourgin, UMR 1318 INRA/CNRS INRA Centre de Versailles-Grignon Route de St-Cyr (RD10), 78026 Versailles Cedex, France. 3Laboratoire Mécanismes Adaptatifs et Evolution, UMR 7179 MNHN/CNRS, CP 55, 57 rue Cuvier 75231 Paris cedex 05, France. 4Département de Géosciences, Université de Fribourg, Ch. du Musée 6, 1700 Fribourg, CH Abstract. We describe a general biophysical mechanism underlying sensory organ formation.
    [Show full text]
  • In Early Development of the Rat Mrna for the Major Myelin Protein
    DEVELOPMENTALDYNAMICS222:40–51(2001) InEarlyDevelopmentoftheRatmRNAfortheMajor MyelinProteinP0 IsExpressedinNonsensoryAreasof theEmbryonicInnerEar,Notochord,EntericNervous System,andOlfactoryEnsheathingCells MENG-JENLEE,1 ESTERCALLE,1 ANGELABRENNAN,1 SABRINAAHMED,1 ELENASVIDERSKAYA,2 1 1 KRISTJANR.JESSEN, ANDRHONAMIRSKY * 1DepartmentofAnatomyandDevelopmentalBiology,UniversityCollegeLondon,London,UnitedKingdom 2DepartmentofAnatomy,StGeorge’sHospitalMedicalSchool,London,UnitedKingdom ABSTRACT ThemyelinproteinP0 hasama- INTRODUCTION jorstructuralroleinSchwanncellmyelin,andthe TheP0 geneandthemechanismsthatcontrolithave expressionofP0 proteinandmRNAinthe beenofgreatinteresteversinceitwasrealizedthatP0 Schwanncelllineagehasbeenextensivelydocu- proteinwasbyfarthemostabundantproteinofmyelin mented.Weshowhere,usinginsituhybridization, inthePNS,andthatitsexpressionwassubjectto thattheP0 geneisalsoactivatedinanumberof dramaticregulationbysignalsfromneurons(Gieseet othertissuesduringembryonicdevelopment.P0 al.,1992;LemkeandAxel,1985;SommerandSuter, mRNAisfirstdetectablein10-day-oldembryos 1998).Inmammals,P0 appearedinitiallytobean (E10)andisatthistimeseenonlyincellsinthe exampleparexcellenceofacelltypespecificgene, cephalicneuralcrestandintheoticplacode/pit.P0 beingrestrictedtothoseSchwanncellsinducedtoform expressioncontinuesintheoticvesicleandatE12 myelinsheaths(Colmanetal.,2001).Ithasnowbe- P0 expressioninthisstructurelargelyoverlaps comeclearthattheP0 geneisactivated,albeitatrel- withexpressionofanothermyelingene,proteo- ativelylowlevels,priortomyelinationnotonlyinall
    [Show full text]
  • Prorhombomeric Subdivision of the Mammalian Embryonic Hindbrain: Is It Functionally Meaningful?
    Int..I. Dc\". Riol. -JI; 213-222 (1997) 213 Prorhombomeric subdivision of the mammalian embryonic hindbrain: is it functionally meaningful? ESTHER RUBERTE', HEATHER B. WOOD' and GilLIAN M. MORRISS-KAY' Department of Human Anatomy, Oxford University, Oxford, United Kingdom ABSTRACT The technique of whole embryo culture has made significant contributions to understanding the mechanisms of morphogenesis in mammalian embryos, especially with respect to cranial neurulation and neural crest cell migration. This study traces the fate of two specifically mammalian structures, the preotic and otic sulci. Their formation at the 1/2- and 3-somite stages respectively, divides the hindbrain neuroepithelium into prorhombomeres A, Band C. The preotic sulcus is a deeply recessed structure that forms the rostral boundary of expression of both Hoxb-2and the first domain of Krox-20. The otic sulcus is a shallow concavity in which the second Krox-20domain is expressed, Dillabeling followed by whole embryo culture confirmed that the later fate of the preotic sulcus is the rhombomere 2/3 boundary, and the fate of the otic sulcus is the cranial part of rhombomere 5. Structurally, the preotic and otic sulci show no specialization with respect to actin, tubulin or proteoglycans, buttheir maintenance depends on contact with the subjacent mesenchyme. Their formation is inhibited by exposure of embryos to retinoic acid prior to the onset of somitic segmentation, indicating that the molecular events governing prorhombomeric subdivision of the hindbrain are retinoic acid-sensitive. The preotic sulcus may be essential for neuroepithelial cell movement towards and into the rapidly enlarging forebrain; the otic sulcus may simply delineate the caudal boundary of prorhombomere B, an area with a discrete neural crest cell population discontinuous with those rostral and caudal to it.
    [Show full text]
  • Cardiac Neural Crest Migration in Chicken Embryos
    Dissertation Approved By Major Advisor Philip R. Brauer, Ph.D., Associate Professor of Biomedical Sciences Barbara Braden, Ph.D. MATRIX METALLOPROTEINASE ACTIVITY IS AN IMPORTANT MEDIATOR OF CARDIAC NEURAL CREST CELL MIGRATION By Dong Hong Cai A DISSERTATION Submitted to the Faculty of the Graduate School of Creighton University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Department of Biomedical Sciences Omaha, Nebraska, December, 2001 II This Dissertation Is Dedicated to: My Dear Wife Hong Tao and My Coming Son III Acknowledgments I would like to express my sincere acknowledgment to my major advisor, Dr. Philip R. Brauer, for his guidance, encouragement, and patience throughout all these years. His compassion for science and thirst for knowledge has deeply impressed me. I would like to thank my committee members Dr. John A. Yee, Dr. Robert Mackin, and Dr. Margaret scofield, for their guidance via numerous discussions and for their generosity to let me use their facilities. I would like to thank my former committee member Dr. Thomas M. Vollberg who trained me in molecular biology and generously provided me his lab facilities during my first two years in this department. I would like to thank Dr. James P. Quigley for providing MMP-2 and TIMP-2 cDNA used in this program. 1 would like to thank my parents and my wife for their support and love over the years. Finally, I would like to thank all my friends and colleagues in this department who provided numerous helps whenever help was needed. IV ABSTRACT Matrix metalloproteinases (MMPs) are a family of zinc proteolytic enzymes important in embryonic development and pathological processes.
    [Show full text]
  • The Neural Crest and Craniofacial Malformations
    Chapter 5 The Neural Crest and Craniofacial Malformations Hans J.ten Donkelaar and Christl Vermeij-Keers 5.1 Introduction the head (Vermeij-Keers 1990; Sulik 1996; LaBonne and Bronner-Fraser 1999; Le Douarin and Kalcheim The neural crest is a temporary embryonic structure 1999; Sperber 2002; Knecht and Bronner-Fraser 2002; that is composed of a population of multipotent cells Francis-West et al. 2003; Santagati and Rijli 2003). In that delaminate from the ectoderm by epitheliomes- addition, during later developmental stages multiple enchymal tranformation (EMT; Duband et al. 1995; places of EMT are recognized as well. In the head– Hay 1995; Le Douarin and Kalcheim 1999; Francis- neck area, for example, the neurogenic placodes and West et al. 2003). Neural-crest-derived cells are called the optic neural crest are such areas. Neurogenic pla- mesectodermal or ectomesenchymal cells (mesoder- codes, specialized regions of the embryonic ecto- mal cells of ectodermal origin) that have arisen derm, are the major source of primary sensory neu- through EMT. The neural crest was first described rons in the head (Johnston and Bronsky 1995; Gra- by His (1868) in the chick embryo as a Zwischen- ham and Begbie 2000). The vasculature of the head is strang, a strip of cells lying between the dorsal ecto- derived from mesoderm-derived endothelial precur- derm and the neural tube. Classic contributions in sors,while the neural crest provides the pericytes and amphibians identified interactions between tissues smooth muscle cells of the vessels of the face and the that lead to neural crest formation, and were re- forebrain (Etchevers et al.
    [Show full text]