DEVELOPMENT OF THE NERVOUS SYSTEM SECOND EDITION DEVELOPMENT OF THE NERVOUS SYSTEM SECOND EDITION DAN H. SANES THOMAS A. REH WILLIAM A. HARRIS Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo Academic Press is an imprint of Elsevier Elsevier Academic Press 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright © 2006, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, E-mail: To our families Contents Preface for the First Edition xi Cell Interactions Control the Number of Cells Made by Preface for the Second Edition xiii Progenitors 63 The Generation of Neurons and GLIA 69 Cerebral Cortex Histogenesis 71 1. Neural Induction 1 The Subventricular Zone: A Secondary Zone of Neurogenesis 75 Development and Evolution of Neurons 1 Cerebellar Cortex Histogenesis 76 Early Embryology of Metazoans 1 Molecular Mechanisms of Neuronal Migration 78 Derivation of Neural Tissue 3 Postembryonic and Adult Neurogenesis 82 Interactions with Neighboring Tissues in Making Neural Summary 85 Tissue 9 The Molecular Nature of the Neural Inducer 13 Conservation of Neural Induction 16 4. Determination and Differentiation 87 Interactions Among the Ectodermal Cells in Controlling Neuroblast Segregation 20 Transcriptional Hierarchies in Invariant Lineages 88 Notch, Delta, and Achaete Scute Genes in Vertebrates 25 Spatial and Temporal Coordinates of Determination 91 Linking Induction to Proneural Activity 27 Asymmetric Cell Divisions and Asymmetric Fate 93 Summary 28 Generating Complexity through Cellular Interactions 94 Specification and Differentiation through Cellular Interactions and Interactions with the Local 2. Polarity and Segmentation 29 Environment 97 Competence and Histogenesis 100 Regional Identity of the Nervous System 29 The Interplay of Intrinsic and Extrinsic Influences in The Anterior-Posterior Axis and HOX Genes 30 Histogenesis 102 HOX Gene Function in the Nervous System 33 Interpreting Gradients and the Spatial Organization of Signaling Molecules that Pattern the Anterior-Posterior Cell Types 106 Axis in Vertebrates: Heads or Tails 36 Summary 109 Organizing Centers in the Developing Brain 39 Forebrain Development, Prosomeres, and PAX Genes 42 Dorsal-Ventral Polarity in the Neural Tube 46 5. Axon Growth and Guidance 111 Dorsal Neural Tube and Neural Crest 50 Patterning the Cerebral Cortex 52 The Growth Cone 114 Summary 55 The Dynamic Cytoskeleton 116 What Do Growth Cones Grow On? 121 3. Genesis and Migration 57 What Provides Directional Information to Growth Cones? 123 Cell-Cycle Genes Control the Number of Neurons Cell Adhesion and Labeled Pathways 124 Generated during Development 62 Repulsive Guidance 127 vii viii CONTENTS Chemotaxis, Gradients, and Local Information 130 Converting Growth Cones to Presynaptic Terminals 221 The Optic Pathway 133 Receptor Clustering Signifies Postsynaptic Differentiation The Midline 134 at NMJ 222 Attraction and Repulsion: Desensitization and Presynaptic Terminals Induce Receptor Aggregation 224 Adaptation 134 Agrin, a Transynaptic Clustering Signal 226 Signal Transduction 137 Postsynaptic Response to Agrin 227 Summary 138 Receptor Clustering Signals in the CNS 229 Internal Membrane Proteins and Receptor Aggregation in the CNS 230 6. Target Selection 145 The Expression and Insertion of New Receptors 233 Neuronal Activity Regulates Receptor Expression 235 Defasiculation 145 Neuregulin, a Regulator of Postsynaptic Target Recognition and Entry 147 Transcription 236 Slowing Down and Branching 148 Maturation of Transmission and Receptor Isoform Border Patrol and Prevention of Inappropriate Transitions 238 Targeting 149 Maturation of Transmitter Reuptake 241 Topographic Mapping 152 Short-Term Plasticity 242 Chemospecificity and Ephrins 153 Appearance of Synaptic Inhibition 243 Shifting and Fine Tuning of Connections 158 Is Inhibition Really Inhibitory during Development? 243 The Third Dimension, Lamina-Specific Summary 244 Termination 162 Cellular and Synaptic Targeting 164 Sniffing Out Targets 166 9. Refinement of Synaptic Connections 247 Summary 170 The Early Pattern of Connections 247 Functional Synapses are Eliminated 249 7. Naturally Occurring Neuron Death 173 Axonal Arbors are Refined or Eliminated 250 Some Terminals Expand or Remain Stable 255 What does Neuron Death Look Like? 173 Neural Activity Regulates Synaptic Connections 255 Early Elimination of Progenitor Cells 174 Sensory Coding Properties Reflect Synapse How Many Differentiated Neurons Die? 174 Rearrangement 262 Survival Depends on the Synaptic Target 176 Activity Contributes to the Alignment of Sensory NGF: A Target-Derived Survival Factor 180 Maps 265 The Neurotrophin Family 182 Spontaneous Activity and Afferent Segregation 267 The TRK Family of Neurotrophin Receptors 184 Many Forms of Plasticity have a Time Limit 271 How does the Neurotrophin Signal Reach the Synapses Interact Over a Short Distance 271 Soma? 186 Heterosynaptic Depression 272 The P75 Neurotrophin Receptor 186 Postsynaptic Receptors are Eliminated 274 The Expanding World of Survival Factors 188 Involvement of Intracellular Calcium 276 Endocrine Control of Cell Survival 190 NMDA Receptors and Calcium Signaling 276 Cell Death Requires Protein Synthesis 192 The Role of Second Messenger Systems 278 Intracellular Signaling 193 Metabotropic Receptors 279 Caspases: Agents of Death 196 Gain Control 280 BCL-2 Proteins: Regulators of Apoptosis 200 Silent Synapses 282 Synaptic Transmission at the Target 201 Homeostasis: The More Things Change, the More They Afferent Regulation of Cell Survival 202 Stay the Same 283 Summary 206 Plasticity of Inhibitory Connections 284 Synaptic Influence on Neuron Morphology 285 Summary 287 8. Synapse Formation and Function 207 What Do Newly Formed Synapses Look Like? 211 10. Behavioral Development 289 The First Signs of Synapse Function 215 The Decision to Form a Synapse 218 Behavioral Ontogeny 289 The Sticky Synapse 220 Genetic and Environmental Mechanisms 290 CONTENTS ix Environmental Determinants of Behavioral Hormonal Signals 306 Development 291 Hormonal Control of Brain Gender 307 The First Movements 291 Genetic Control of Brain Gender 308 The Mechanism of Spontaneous Movements 293 Singing in the Brain 309 Embryonic Movements: Uncoordinated or Integrated? 294 From Gonads to Brain? 310 The Role of Activity in the Emergence of Coordinated Learning to Remember 311 Behavior 296 Where’s Mamma? 312 Stage-Specific Behaviors 297 Fear and Loathing 314 Beginning to Make Sense of the World 299 Getting Information from One Brain to Another 317 Asking Babies Questions 300 Language 319 Sharp Eyesight 301 Summary 321 Acute Hearing 302 Sex-Specific Behavior 305 References 323 Genetic Sex 306 Index 361