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 fr.