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Building Brains: An Introduction to Neural Development, 2nd Edition

Building Brains: An Introduction to Neural Development, 2nd Edition

David J. Price, Andrew P. Jarman, John O. Mason, Peter C. Kind

ISBN: 978-1-119-29388-0

Nov 2017

384 pages


Provides a highly visual, readily accessible introduction to the main events that occur during neural development and their mechanisms

Building Brains: An Introduction to Neural Development, 2nd Edition describes how brains construct themselves, from simple beginnings in the early embryo to become the most complex living structures on the planet. It explains how cells first become neural, how their proliferation is controlled, what regulates the types of neural cells they become, how neurons connect to each other, how these connections are later refined under the influence of neural activity, and why some neurons normally die. This student-friendly guide stresses and justifies the generally-held belief that a greater knowledge of how nervous systems construct themselves will help us find new ways of treating diseases of the nervous system that are thought to originate from faulty development, such as autism spectrum disorders, epilepsy, and schizophrenia.

  • A concise, illustrated guide focusing on core elements and emphasizing common principles of developmental mechanisms, supplemented by suggestions for further reading
  • Text boxes provide detail on major advances, issues of particular uncertainty or controversy, and examples of human diseases that result from abnormal development
  • Introduces the methods for studying neural development, allowing the reader to understand the main evidence underlying research advances
  • Offers a balanced mammalian/non-mammalian perspective (and emphasizes mechanisms that are conserved across species), drawing on examples from model organisms like the fruit fly, nematode worm, frog, zebrafish, chick, mouse and human
  • Associated Website includes all the figures from the textbook and explanatory movies

Filled with full-colorartwork that reinforces important concepts; an extensive glossary and definitions that help readers from different backgrounds; and chapter summaries that stress important points and aid revision, Building Brains: An Introduction to Neural Development, 2nd Edition is perfect for undergraduate students and postgraduates who may not have a background in neuroscience and/or molecular genetics.

“This elegant book ranges with ease and authority over the vast field of developmental neuroscience. This excellent textbook should be on the shelf of every neuroscientist, as well as on the reading list of every neuroscience student.” 
—Sir Colin Blakemore, Oxford University

“With an extensive use of clear and colorful illustrations, this book makes accessible to undergraduates the beauty and complexity of neural development. The book fills a void in undergraduate neuroscience curricula.”
—Professor Mark Bear, Picower Institute, MIT.

Highly Commended, British Medical Association Medical Book Awards 2012

Published with the New York Academy of Sciences

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Preface to Second Edition xi

Preface to First Edition xiii

Conventions and Commonly used Abbreviations xv

Introduction xix

About the Companion Website xxiii

1 Models and Methods for Studying Neural Development 1

1.1 What is neural development? 1

1.2 Why research neural development? 2

The uncertainty of current understanding 2

Implications for human health 3

Implications for future technologies 4

1.3 Major breakthroughs that have contributed to understanding developmental mechanisms 4

1.4 Invertebrate model organisms 5

Fly 5

Worm 7

Other invertebrates 11

1.5 Vertebrate model organisms 11

Frog 11

Chick 12

Zebrafish 12

Mouse 12

Humans 19

Other vertebrates 20

1.6 Observation and experiment: methods for studying neural development 23

1.7 Summary 24

2 The Anatomy of Developing Nervous Systems 25

2.1 The nervous system develops from the embryonic neuroectoderm 25

2.2 Anatomical terms used to describe locations in embryos 26

2.3 Development of the neuroectoderm of invertebrates 27

C. elegans 27

Drosophila 27

2.4 Development of the neuroectoderm of vertebrates and the process of neurulation 30

Frog 31

Chick 33

Zebrafish 35

Mouse 36

Human 43

2.5 Secondary neurulation in vertebrates 47

2.6 Formation of invertebrate and vertebrate peripheral nervous systems 47

Invertebrates 49

Vertebrates: the neural crest and the placodes 49

Vertebrates: development of sense organs 50

2.7 Summary 52

3 Neural Induction: An Example of How Intercellular Signalling Determines Cell Fates 53

3.1 What is neural induction? 53

3.2 Specification and commitment 54

3.3 The discovery of neural induction 54

3.4 A more recent breakthrough: identifying molecules that mediate neural induction 56

3.5 Conservation of neural induction mechanisms in Drosophila 58

3.6 Beyond the default model – other signalling pathways involved in neural induction 59

3.7 Signal transduction: how cells respond to intercellular signals 64

3.8 Intercellular signalling regulates gene expression 65

General mechanisms of transcriptional regulation 65

Transcription factors involved in neural induction 67

What genes do transcription factors control? 69

Gene function can also be controlled by other mechanisms 71

3.9 The essence of development: a complex interplay of intercellular and intracellular signalling 75

3.10 Summary 75

4 Patterning the Neuroectoderm 77

4.1 Regional patterning of the nervous system 77

Patterns of gene expression are set up by morphogens 78

Patterning happens progressively 80

4.2 Patterning the anteroposterior (AP) axis of the Drosophila CNS 81

From gradients of signals to domains of transcription factor expression 81

Dividing the ectoderm into segmental units 83

Assigning segmental identity – the Hox code 83

4.3 Patterning the AP axis of the vertebrate CNS 86

Hox genes are highly conserved 87

Initial AP information is imparted by the mesoderm 88

Genes that pattern the anterior brain 90

4.4 Local patterning in Drosophila: refining neural patterning within segments 91

In Drosophila a signalling boundary within each segment provides local AP positional information 92

Patterning in the Drosophila dorsoventral(DV) axis 94

Unique neuroblast identities from the integration of AP and DV patterning information 96

4.5 Local patterning in the vertebrate nervous system 97

In the vertebrate brain, AP boundaries organize local patterning 97

Patterning in the DV axis of the vertebrate CNS 99

Signal gradients that drive DV patterning 100

SHH and BMP are morphogens for DV progenitor domains in the neural tube 101

Integration of AP and DV patterning information 103

4.6 Summary 103

5 Neurogenesis: Generating Neural Cells 105

5.1 Generating neural cells 105

5.2 Neurogenesis in Drosophila 106

Proneural genes promote neural commitment 106

Lateral inhibition: Notch signalling inhibits commitment 106

5.3 Neurogenesis in vertebrates 107

Proneural genes are conserved 107

In the vertebrate CNS, neurogenesis involves radial glial cells 111

Proneural factors and Notch signaling in the vertebrate CNS 111

5.4 The regulation of neuronal subtype identity 114

Different proneural genes – different programmes of neurogenesis 114

Combinatorial control by transcription factors creates neuronal diversity 114

5.5 The regulation of cell proliferation during neurogenesis 117

Signals that promote proliferation 117

Cell division patterns during neurogenesis 118

Asymmetric cell division in Drosophila requires Numb 118

Control of asymmetric cell division in vertebrate neurogenesis 121

In vertebrates, division patterns are regulated to generate vast numbers of neurons 122

5.6 Temporal regulation of neural identity 124

A neural cell’s time of birth is important for neural identity 124

Time of birth can generate spatial patterns of neurons 126

How does birth date influence a neurons fate? 128

Intrinsic mechanism of temporal control in Drosophila neuroblasts 128

Birth date, lamination and competence in the mammalian cortex 129

5.7 Why do we need to know about neurogenesis? 133

5.8 Summary 133

6 How Neurons Develop Their Shapes 135

6.1 Neurons form two specialized types

of outgrowth 135

Axons and dendrites 135

The cytoskeleton in mature axons and dendrites 137

6.2 The growing neurite 138

A neurite extends by growth at its tip 138

Mechanisms of growth cone dynamics 139

6.3 Stages of neurite outgrowth 141

Neurite outgrowth in cultured hippocampal neuron 141

Neurite outgrowth in vivo 142

6.4 Neurite outgrowth is influenced by a neuron’s surroundings 143

The importance of extracellular cues 143

Extracellular signals that promote or inhibit neurite outgrowth 143

6.5 Molecular responses in the growth cone 145

Key intracellular signal transduction events 145

Small G proteins are critical regulators of neurite growth 145

Effector molecules directly influence actin filament dynamics 147

Regulation of other processes in the extending neurite 148

6.6 Active transport along the axon is

important for outgrowth 149

6.7 The developmental regulation

of neuronal polarity 149

Signalling during axon specification 149

Ensuring there is just one axon 151

Which neurite becomes the axon? 152

6.8 Dendrites 153

Regulation of dendrite branching 153

Dendrite branches undergo

self]avoidance 154

Dendritic fields exhibit tiling 155

6.9 Summary 156

7 Neuronal Migration 157

7.1 Many neurons migrate long distances during formation of the nervous system 157

7.2 How can neuronal migration be observed? 157

Watching neurons move in living embryos 158

Observing migrating neurons in cultured tissues 158

Tracking cell migration by indirect methods 158

7.3 Major modes of migration 164

Some migrating neurons are guided by a scaffold 164

Some neurons migrate in groups 165

Some neurons migrate individually 168

7.4 Initiation of migration 169

Initiation of neural crest cell migration 170

Initiation of neuronal migration 170

7.5 How are migrating cells guided to their destinations? 170

Directional migration of neurons in C. elegans 171

Guidance of neural crest cell migration 173

Guidance of neural precursors in the developing lateral line of zebrafish 174

Guidance by radial glial fibres 174

7.6 Locomotion 176

7.7 Journey’s end – termination of migration 179

7.8 Embryonic cerebral cortex contains both radially and tangentially migrating cells 182

7.9 Summary 184

8 Axon Guidance 185

8.1 Many axons navigate long and complex routes 185

How might axons be guided to their targets? 185

The growth cone 187

Breaking the journey – intermediate targets 188

8.2 Contact guidance 190

Contact guidance in action: pioneers and followers, fasciculation and defasciculation 191

Ephs and ephrins: versatile cell surface molecules with roles in contact guidance 191

8.3 Guidance of axons by diffusible cues – chemotropism 194

Netrin – a chemotropic cue expressed at the ventral midline 195

Slits 195

Semaphorins 198

Other axon guidance molecules 198

8.4 How do axons change their behavior at choice points? 199

Commissural axons lose their attraction to netrin once they have crossed the floor plate 199

Putting it all together – guidance cues and their receptors choreograph commissural axon pathfinding at the ventral midline 202

After crossing the midline, commissural axons project towards the brain 205

8.5 How can such a small number of cues guide such a large number of axons? 207

The same guidance cues are deployed in multiple axon pathways 208

Interactions between guidance cues and their receptors can be altered by co]factors 208

8.6 Some axons form specific connections over very short distances, probably using different mechanisms 209

8.7 The growth cone has autonomy in its ability to respond to guidance cues 209

Growth cones can still navigate when severed from their cell bodies 209

Local translation in growth cones 210

8.8 Transcription factors regulate axon guidance decisions 211

8.9 Summary 212

9 Life and Death in the Developing Nervous System 215

9.1 The frequency and function of cell death during normal development 215

9.2 Cells die in one of two main ways: apoptosis or necrosis 217

9.3 Studies in invertebrates have taught us much about how cells kill themselves 219

The specification phase 221

The killing phase 221

The engulfment phase 222

9.4 Most of the genes that regulate programmed cell death in C. elegans are conserved in vertebrates 222

9.5 Examples of neurodevelopmental processes in which programmed cell death plays a prominent role 224

Programmed cell death in early progenitor cell populations 224

Programmed cell death contributes to sexual differences in the nervous system 225

Programmed cell death removes cells with transient functions once their task is done 227

Programmed cell death matches the numbers of cells in interacting neural tissues 230

9.6 Neurotrophic factors are important regulators of cell survival and death 232

Growth factors 232

Cytokines 235

9.7 A role for electrical activity in regulating programmed cell death 235

9.8 Summary 237

10 Map Formation 239

10.1 What are maps? 239

10.2 Types of maps 239

Coarse maps 241

Fine maps 242

10.3 Principles of map formation 243

Axon order during development 244

Theories of map formation 245

10.4 Development of coarse maps: cortical areas 246

Protomap versus protocortex 246

Spatial position of cortical areas 247

10.5 Development of fine maps: topographic 248

Retinotectal pathways 248

Sperry and the chemoaffinity hypothesis 250

Ephrins act as molecular postcodes in the chick tectum 252

10.6 Inputs from multiple structures: when maps collide 253

From retina to cortex in mammals 254

Activity]dependent eye]specific segregation: a role for retinal waves 254

Formation of ocular dominance bands 257

Ocular dominance bands form by directed In growth of thalamocortical axons 257

Activity and the formation of ocular dominance bands 259

Integration of sensory maps 260

10.7 Development of feature maps 261

Feature maps in the visual system 261

Role of experience in orientation and direction map formation 263

10.8 Summary 264

11 Maturation of Functional

Properties 265

11.1 Neurons are excitable cells 266

What makes a cell excitable? 266

Electrical properties of neurons 267

Regulation of intrinsic neuronal

physiology 269

11.2 Neuronal excitability during development 271

Neuronal excitability changes dramatically during development 271

Early action potentials are driven by Ca2+, not Na+ 271

Neurotransmitter receptors regulate excitability prior to synapse formation 273

GABAergic receptor activation switches from being excitatory to inhibitory 273

11.3 Developmental processes regulated by neuronal excitability 275

Electrical excitability regulates neuronal proliferation and migration 275

Neuronal activity and axon guidance 277

11.4 Synaptogenesis 277

The synapse 278

Electrical properties of dendrites 278

Stages of synaptogenesis 280

Synaptic specification and induction 281

Synapse formation 285

Synapse selection: stabilization and withdrawal 286

11.5 Spinogenesis 286

Spine shape and dynamics 287

Theories of spinogenesis 289

Mouse models of spinogenesis: the weaver mutant 290

Molecular regulators of spine development 291

11.6 Summary 293

12 Experience]Dependent Development 295

12.1 Effects of experience on visual system development 296

Seeing one world with two eyes: ocular dominance of cortical cells 296

Visual experience regulates ocular dominance 297

Competition regulates experiencedependent plasticity: the effects of darkrearing and strabismus 299

Physiological changes in ocular dominance prior to anatomical changes 301

Cooperative binocular interactions and visual cortex plasticity 304

The timing of developmental plasticity: sensitive or critical periods 305

Multiple sensitive periods in the developing visual system 306

12.2 How does experience change functional connectivity? 307

Cellular basis of plasticity: synaptic strengthening and weakening 309

The time]course of changes in synaptic weight in response to monocular deprivation 310

Cellular and molecular mechanisms of LTP/LTD induction 312

Synaptic changes that mediate the expression of LTP/LTD and experiencedependent plasticity 314 Metaplasticity 318

Spike]timing dependent plasticity 320

12.3 Cellular basis of plasticity: development of inhibitory networks 322

Inhibition contributes to the expression of the effects of monocular deprivation 322

Development of inhibitory circuits regulates the time]course of the sensitive period for monocular deprivation 323

12.4 Homeostatic plasticity 324

Mechanisms of homeostatic plasticity 325

12.5 Structural plasticity and the role of the extracellular matrix 327

12.6 Summary 328

Glossary 329

Index 349