Building Brains

DAVID J. PRICE, ANDREW P. JARMAN, JOHN O. MASON, PETER C. KIND, Centre for Integrative Physiology, University of Edinburgh, UK.

• Preface to Second Edition xiPreface to First Edition xiiiConventions and Commonly used Abbreviations xvIntroduction xixAbout the Companion Website xxiii1 Models and Methods for Studying Neural Development 11.1 What is neural development? 11.2 Why research neural development? 2The uncertainty of current understanding 2Implications for human health 3Implications for future technologies 41.3 Major breakthroughs that have contributed to understanding developmental mechanisms 41.4 Invertebrate model organisms 5Fly 5Worm 7Other invertebrates 111.5 Vertebrate model organisms 11Frog 11Chick 12Zebrafish 12Mouse 12Humans 19Other vertebrates 201.6 Observation and experiment: methods for studying neural development 231.7 Summary 242 The Anatomy of Developing Nervous Systems 252.1 The nervous system develops from the embryonic neuroectoderm 252.2 Anatomical terms used to describe locations in embryos 262.3 Development of the neuroectoderm of invertebrates 27C. elegans 27Drosophila 272.4 Development of the neuroectoderm of vertebrates and the process of neurulation 30Frog 31Chick 33Zebrafish 35Mouse 36Human 432.5 Secondary neurulation in vertebrates 472.6 Formation of invertebrate and vertebrate peripheral nervous systems 47Invertebrates 49Vertebrates: the neural crest and the placodes 49Vertebrates: development of sense organs 502.7 Summary 523 Neural Induction: An Example of How Intercellular Signalling Determines Cell Fates 533.1 What is neural induction? 533.2 Specification and commitment 543.3 The discovery of neural induction 543.4 A more recent breakthrough: identifying molecules that mediate neural induction 563.5 Conservation of neural induction mechanisms in Drosophila 583.6 Beyond the default model – other signalling pathways involved in neural induction 593.7 Signal transduction: how cells respond to intercellular signals 643.8 Intercellular signalling regulates gene expression 65General mechanisms of transcriptional regulation 65Transcription factors involved in neural induction 67What genes do transcription factors control? 69Gene function can also be controlled by other mechanisms 713.9 The essence of development: a complex interplay of intercellular and intracellular signalling 753.10 Summary 754 Patterning the Neuroectoderm 774.1 Regional patterning of the nervous system 77Patterns of gene expression are set up by morphogens 78Patterning happens progressively 804.2 Patterning the anteroposterior (AP) axis of the Drosophila CNS 81From gradients of signals to domains of transcription factor expression 81Dividing the ectoderm into segmental units 83Assigning segmental identity – the Hox code 834.3 Patterning the AP axis of the vertebrate CNS 86Hox genes are highly conserved 87Initial AP information is imparted by the mesoderm 88Genes that pattern the anterior brain 904.4 Local patterning in Drosophila: refining neural patterning within segments 91In Drosophila a signalling boundary within each segment provides local AP positional information 92Patterning in the Drosophila dorsoventral(DV) axis 94Unique neuroblast identities from the integration of AP and DV patterning information 964.5 Local patterning in the vertebrate nervous system 97In the vertebrate brain, AP boundaries organize local patterning 97Patterning in the DV axis of the vertebrate CNS 99Signal gradients that drive DV patterning 100SHH and BMP are morphogens for DV progenitor domains in the neural tube 101Integration of AP and DV patterning information 1034.6 Summary 1035 Neurogenesis: Generating Neural Cells 1055.1 Generating neural cells 1055.2 Neurogenesis in Drosophila 106Proneural genes promote neural commitment 106Lateral inhibition: Notch signalling inhibits commitment 1065.3 Neurogenesis in vertebrates 107Proneural genes are conserved 107In the vertebrate CNS, neurogenesis involves radial glial cells 111Proneural factors and Notch signaling in the vertebrate CNS 1115.4 The regulation of neuronal subtype identity 114Different proneural genes – different programmes of neurogenesis 114Combinatorial control by transcription factors creates neuronal diversity 1145.5 The regulation of cell proliferation during neurogenesis 117Signals that promote proliferation 117Cell division patterns during neurogenesis 118Asymmetric cell division in Drosophila requires Numb 118Control of asymmetric cell division in vertebrate neurogenesis 121In vertebrates, division patterns are regulated to generate vast numbers of neurons 1225.6 Temporal regulation of neural identity 124A neural cell’s time of birth is important for neural identity 124Time of birth can generate spatial patterns of neurons 126How does birth date influence a neurons fate? 128Intrinsic mechanism of temporal control in Drosophila neuroblasts 128Birth date, lamination and competence in the mammalian cortex 1295.7 Why do we need to know about neurogenesis? 1335.8 Summary 1336 How Neurons Develop Their Shapes 1356.1 Neurons form two specialized typesof outgrowth 135Axons and dendrites 135The cytoskeleton in mature axons and dendrites 1376.2 The growing neurite 138A neurite extends by growth at its tip 138Mechanisms of growth cone dynamics 1396.3 Stages of neurite outgrowth 141Neurite outgrowth in cultured hippocampal neuron 141Neurite outgrowth in vivo 1426.4 Neurite outgrowth is influenced by a neuron’s surroundings 143The importance of extracellular cues 143Extracellular signals that promote or inhibit neurite outgrowth 1436.5 Molecular responses in the growth cone 145Key intracellular signal transduction events 145Small G proteins are critical regulators of neurite growth 145Effector molecules directly influence actin filament dynamics 147Regulation of other processes in the extending neurite 1486.6 Active transport along the axon isimportant for outgrowth 1496.7 The developmental regulationof neuronal polarity 149Signalling during axon specification 149Ensuring there is just one axon 151Which neurite becomes the axon? 1526.8 Dendrites 153Regulation of dendrite branching 153Dendrite branches undergoself]avoidance 154Dendritic fields exhibit tiling 1556.9 Summary 1567 Neuronal Migration 1577.1 Many neurons migrate long distances during formation of the nervous system 1577.2 How can neuronal migration be observed? 157Watching neurons move in living embryos 158Observing migrating neurons in cultured tissues 158Tracking cell migration by indirect methods 1587.3 Major modes of migration 164Some migrating neurons are guided by a scaffold 164Some neurons migrate in groups 165Some neurons migrate individually 1687.4 Initiation of migration 169Initiation of neural crest cell migration 170Initiation of neuronal migration 1707.5 How are migrating cells guided to their destinations? 170Directional migration of neurons in C. elegans 171Guidance of neural crest cell migration 173Guidance of neural precursors in the developing lateral line of zebrafish 174Guidance by radial glial fibres 1747.6 Locomotion 1767.7 Journey’s end – termination of migration 1797.8 Embryonic cerebral cortex contains both radially and tangentially migrating cells 1827.9 Summary 1848 Axon Guidance 1858.1 Many axons navigate long and complex routes 185How might axons be guided to their targets? 185The growth cone 187Breaking the journey – intermediate targets 1888.2 Contact guidance 190Contact guidance in action: pioneers and followers, fasciculation and defasciculation 191Ephs and ephrins: versatile cell surface molecules with roles in contact guidance 1918.3 Guidance of axons by diffusible cues – chemotropism 194Netrin – a chemotropic cue expressed at the ventral midline 195Slits 195Semaphorins 198Other axon guidance molecules 1988.4 How do axons change their behavior at choice points? 199Commissural axons lose their attraction to netrin once they have crossed the floor plate 199Putting it all together – guidance cues and their receptors choreograph commissural axon pathfinding at the ventral midline 202After crossing the midline, commissural axons project towards the brain 2058.5 How can such a small number of cues guide such a large number of axons? 207The same guidance cues are deployed in multiple axon pathways 208Interactions between guidance cues and their receptors can be altered by co]factors 2088.6 Some axons form specific connections over very short distances, probably using different mechanisms 2098.7 The growth cone has autonomy in its ability to respond to guidance cues 209Growth cones can still navigate when severed from their cell bodies 209Local translation in growth cones 2108.8 Transcription factors regulate axon guidance decisions 2118.9 Summary 2129 Life and Death in the Developing Nervous System 2159.1 The frequency and function of cell death during normal development 2159.2 Cells die in one of two main ways: apoptosis or necrosis 2179.3 Studies in invertebrates have taught us much about how cells kill themselves 219The specification phase 221The killing phase 221The engulfment phase 2229.4 Most of the genes that regulate programmed cell death in C. elegans are conserved in vertebrates 2229.5 Examples of neurodevelopmental processes in which programmed cell death plays a prominent role 224Programmed cell death in early progenitor cell populations 224Programmed cell death contributes to sexual differences in the nervous system 225Programmed cell death removes cells with transient functions once their task is done 227Programmed cell death matches the numbers of cells in interacting neural tissues 2309.6 Neurotrophic factors are important regulators of cell survival and death 232Growth factors 232Cytokines 2359.7 A role for electrical activity in regulating programmed cell death 2359.8 Summary 23710 Map Formation 23910.1 What are maps? 23910.2 Types of maps 239Coarse maps 241Fine maps 24210.3 Principles of map formation 243Axon order during development 244Theories of map formation 24510.4 Development of coarse maps: cortical areas 246Protomap versus protocortex 246Spatial position of cortical areas 24710.5 Development of fine maps: topographic 248Retinotectal pathways 248Sperry and the chemoaffinity hypothesis 250Ephrins act as molecular postcodes in the chick tectum 25210.6 Inputs from multiple structures: when maps collide 253From retina to cortex in mammals 254Activity]dependent eye]specific segregation: a role for retinal waves 254Formation of ocular dominance bands 257Ocular dominance bands form by directed In growth of thalamocortical axons 257Activity and the formation of ocular dominance bands 259Integration of sensory maps 26010.7 Development of feature maps 261Feature maps in the visual system 261Role of experience in orientation and direction map formation 26310.8 Summary 26411 Maturation of FunctionalProperties 26511.1 Neurons are excitable cells 266What makes a cell excitable? 266Electrical properties of neurons 267Regulation of intrinsic neuronalphysiology 26911.2 Neuronal excitability during development 271Neuronal excitability changes dramatically during development 271Early action potentials are driven by Ca2+, not Na+ 271Neurotransmitter receptors regulate excitability prior to synapse formation 273GABAergic receptor activation switches from being excitatory to inhibitory 27311.3 Developmental processes regulated by neuronal excitability 275Electrical excitability regulates neuronal proliferation and migration 275Neuronal activity and axon guidance 27711.4 Synaptogenesis 277The synapse 278Electrical properties of dendrites 278Stages of synaptogenesis 280Synaptic specification and induction 281Synapse formation 285Synapse selection: stabilization and withdrawal 28611.5 Spinogenesis 286Spine shape and dynamics 287Theories of spinogenesis 289Mouse models of spinogenesis: the weaver mutant 290Molecular regulators of spine development 29111.6 Summary 29312 Experience]Dependent Development 29512.1 Effects of experience on visual system development 296Seeing one world with two eyes: ocular dominance of cortical cells 296Visual experience regulates ocular dominance 297Competition regulates experiencedependent plasticity: the effects of darkrearing and strabismus 299Physiological changes in ocular dominance prior to anatomical changes 301Cooperative binocular interactions and visual cortex plasticity 304The timing of developmental plasticity: sensitive or critical periods 305Multiple sensitive periods in the developing visual system 30612.2 How does experience change functional connectivity? 307Cellular basis of plasticity: synaptic strengthening and weakening 309The time]course of changes in synaptic weight in response to monocular deprivation 310Cellular and molecular mechanisms of LTP/LTD induction 312Synaptic changes that mediate the expression of LTP/LTD and experiencedependent plasticity 314 Metaplasticity 318Spike]timing dependent plasticity 32012.3 Cellular basis of plasticity: development of inhibitory networks 322Inhibition contributes to the expression of the effects of monocular deprivation 322Development of inhibitory circuits regulates the time]course of the sensitive period for monocular deprivation 32312.4 Homeostatic plasticity 324Mechanisms of homeostatic plasticity 32512.5 Structural plasticity and the role of the extracellular matrix 32712.6 Summary 328Glossary 329Index 349