Embryos, Genes and Birth Defects

Dr. Patrizia Ferretti. Developmental Biology Unit, Institute of Child Health, University College London. Prof. Andrew Copp (Dean of Institute). Neural Development Unit, Institute of Child Health, University College London.Prof. Cheryll Tickle. Professor of Anatomy & Physiology, The Wellcome Trust Building, University of Dundee.Prof. Gudrun Moore. Institute of Child Health, University College London.The editors are all distinguished developmental biologists with a broad range of expertise in human birth defects. Andrew Copp holds an endowed chair in Developmental Neurobiology at University College London and is Dean of the world-renowned Institute of Child Health.

• Preface to the First Edition ixPreface to the Second Edition xiContributors xiii1. The Relationship between Genotype and Phenotype: Some Basic Concepts 1Philip Stanier and Gudrun MooreIntroduction 1The relationship between genotype and phenotype 2The role of 'model' systems 8The changing concept of homology 92. Uses of Databases in Dysmorphology 19Michael BaraitserWhat is a syndrome? 19Some of these problems are addressed by dysmorphology databases 20Where databases do not help 23Dysmorphology databases 24How databases work 263. Human CytogeneticsJ. D. A. DelhantyIntroduction 33Population cytogenetics 34Structural anomalies 35The genesis of chromosome abnormalities 36Embryo survival 44The cause of high levels of chromosome abnormality in human embryos 44Relative parental risks – age, translocations, inversions, gonadal and germinal mosaics 454. Identification and Analysis of Genes Involved in Congenital Malformation Syndromes 51Peter J. ScamblerGene identification 51Biological analysis of genes implicated in birth defect syndromes 59Animal models 64Why study rare human birth defect syndromes? 705. Transgenic Technology and Its Role in Understanding Normal and Abnormal Mammalian Development 79Valerie Vidal and Andreas SchedlIntroduction 79Transgenic mice 80Genetic manipulation using gene targeting in ES cells 88Outlook and future developments 956. Chemical Teratogens: Hazards, Tools and Clues 99Nigel A. Brown (with revisions by Cheryll TickleIntroduction 99Teratogens and human malformations 100General strategy in chemical teratogenesis 102Valproic acid 102Gene–teratogen interaction 106Teratogens and phenocopies 106Teratogens as manipulative tools 108Teratogens as clues 110Final comments 1177. The Limbs 123Patrizia Ferretti and Cheryll TickleDevelopmental anatomy of the human limb 123Main classes of limb defects 125Contemporary studies on mechanisms of limb development 127Limb regeneration 140How, when and where experimental studies elucidate abnormal development 145Agenda for the future 1518. Brain and Spinal Cord 167Andrew J. CoppIntroduction 167Overview of nervous system development 169Defects of CNS development: towards a genetic and developmental understanding 175Agenda for the future 1929. Birth Defects Affecting the Eye 199Jane C. SowdenThe eye 199Development of the eye 200Congenital eye defects and paediatric blindness 204Gene mutations underlying congenital eye defects 206Cellular and molecular mechanisms affecting eye development and how they elucidate the causes of abnormal development 213Agenda for the future 22010. The Ear 231Sarah Spiden and Karen P. SteelIntroduction 231Development of the outer and middle ear 233Development of the inner ear 234Main classes of ear defects 236Mechanisms involved in development of the outer and middle ear 248Mechanisms underlying inner ear development 249Mechanisms underlying development of inner ear sensory epithelia 251Mechanisms involved in endolymph homeostasis 253The future 25411. Development of the Enteric Nervous System in Relation to Hirschsprung's Disease 263Heather M. Young, Donald F. Newgreen and Alan J. BurnsIntroduction 263Anatomy and function of the ENS 263The best-characterized developmental defect of the ENS – Hirschsprung's disease 265Cell biology of ENS development 266Molecular biology of ENS development and Hirschsprung-like dysplasias 270HSCR: current and future treatments 286Conclusions 28812. The Head 301Gillian M. Morriss-KayIntroduction 301Developmental anatomy 302Main classes of craniofacial defect 371Cellular and molecular mechanisms 321Agenda for the future 33213. The Heart 341Deborah Henderson, Mary R. Hutson and Margaret L. KirbyDevelopmental anatomy 341Major cell populations needed for heart development 345Molecular regulation of heart development 347Cardiovascular defects 356The Future 36214. The Skin 373Ahmad Waseem and Irene M. LeighIntroduction 373Developmental anatomy 374Main classes of skin defects 391Future perspectives 40015. The Vertebral Column 411David Rice and Susanne DietrichIntroduction 411Developmental anatomy of the vertebral column 414Making the vertebral column 421Agenda for the future 44416. The Kidney 463Paul J. D. WinyardIntroduction 463Structure and function 464Developmental anatomy of nephrogenesis 465Transcription factors 473Growth factors and their receptors 479Survival/proliferation factors 487Cell adhesion molecules 488Other molecules 492Non-genetic causes of renal malformations 495Agenda for the future 49917. The Teeth 515Irma ThesleffDevelopmental anatomy 515Main classes of defects 517Cellular and molecular mechanisms affecting development 520How cellular and molecular developmental mechanisms assist in elucidating the causes of abnormal development 525Agenda for the future 529Index 537