| Preface |
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xi | |
| Conventions and Commonly used Abbreviations |
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xiii | |
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1 Models and Methods for Studying Neural Development |
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1 | (18) |
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1.1 What is neural development? |
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1 | (1) |
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1.2 Why research neural development? |
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2 | (2) |
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The uncertainty of current understanding |
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2 | (1) |
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Implications for human health |
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2 | (1) |
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Implications for future technologies |
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3 | (1) |
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1.3 Major breakthroughs that have contributed to understanding developmental mechanisms |
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4 | (1) |
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1.4 Invertebrate model organisms |
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4 | (5) |
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4 | (1) |
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5 | (4) |
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9 | (1) |
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1.5 Vertebrate model organisms |
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9 | (8) |
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9 | (1) |
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10 | (1) |
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10 | (2) |
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12 | (4) |
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16 | (1) |
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16 | (1) |
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1.6 Observation and experiment: methods for studying neural development |
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17 | (1) |
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18 | (1) |
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2 The Anatomy of Developing Nervous Systems |
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19 | (24) |
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2.1 The nervous system develops from the embryonic neuroectoderm |
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19 | (1) |
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2.2 Anatomical terms used to describe locations in embryos |
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20 | (1) |
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2.3 Development of the neuroectoderm of invertebrates |
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21 | (3) |
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21 | (1) |
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21 | (3) |
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2.4 Development of the neuroectoderm of vertebrates and the process of neurulation |
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24 | (12) |
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25 | (2) |
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27 | (2) |
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29 | (7) |
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2.5 Secondary neurulation in vertebrates |
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36 | (1) |
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2.6 Formation of invertebrate and vertebrate peripheral nervous systems |
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37 | (4) |
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37 | (1) |
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Vertebrates: the neural crest and the placodes |
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38 | (2) |
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Vertebrates: development of sense organs |
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40 | (1) |
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41 | (2) |
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3 Neural Induction: An Example of How Intercellular Signalling Determines Cell Fates |
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43 | (22) |
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3.1 What is neural induction? |
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43 | (1) |
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3.2 Specification and commitment |
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44 | (1) |
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3.3 The discovery of neural induction |
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44 | (2) |
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3.4 A more recent breakthrough: identifying molecules that mediate neural induction |
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46 | (3) |
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3.5 Conservation of neural induction mechanisms in Drosophila |
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49 | (1) |
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3.6 Beyond the default model - other signalling pathways involved in neural induction |
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49 | (5) |
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3.7 Signal transduction: how cells respond to intercellular signals |
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54 | (1) |
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3.8 Intercellular signalling regulates gene expression |
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55 | (7) |
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General mechanisms of transcriptional regulation |
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55 | (4) |
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Transcription factors involved in neural induction |
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59 | (1) |
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What genes do transcription factors control? |
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60 | (1) |
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Gene function can also be controlled by other mechanisms |
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60 | (2) |
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3.9 The essence of development: a complex interplay of intercellular and intracellular signalling |
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62 | (1) |
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63 | (2) |
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4 Patterning the Neuroectoderm |
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65 | (26) |
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4.1 Regional patterning of the nervous system |
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65 | (3) |
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Patterns of gene expression are set up by morphogens |
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65 | (1) |
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Patterning occurs within a monolayer epithelium |
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66 | (1) |
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Patterning happens progressively |
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66 | (2) |
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4.2 Patterning the anteroposterior (AP) axis of the Drosophila CNS |
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68 | (2) |
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Creating domains of transcription factor expression |
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68 | (2) |
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Dividing the ectoderm into segmental units |
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70 | (1) |
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Assigning segmental identity - the Hox code |
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70 | (1) |
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4.3 Patterning the AP axis of the vertebrate CNS |
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71 | (8) |
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Hox genes are highly conserved |
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71 | (2) |
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Initial AP information is imparted by the mesoderm |
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73 | (2) |
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Mesoderm signals set up domains of transcription factor expression |
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75 | (1) |
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The hindbrain is organized into segments called rhombomeres |
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76 | (1) |
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How rhombomeres are specified |
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77 | (2) |
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4.4 Refining AP axis patterning within regions and segments |
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79 | (4) |
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Rhombomere cell populations are kept separate by Eph-ephrin signalling |
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79 | (1) |
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Boundaries organize local patterning in Drosophila segments |
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80 | (2) |
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In the vertebrate brain, boundaries organize local patterning |
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82 | (1) |
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4.5 Patterning the dorsoventral (DV) axis of the nervous system |
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83 | (6) |
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Patterns of neurons in the DV axis of the spinal cord |
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83 | (1) |
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Embryonic origin of the DV axis |
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84 | (1) |
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DV neural patterning in Drosophila |
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84 | (2) |
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DV patterning in vertebrates |
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86 | (3) |
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Morphogens set up DV progenitor domains |
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89 | (1) |
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4.6 Bringing it all together |
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89 | (1) |
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90 | (1) |
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5 Neurogenesis: Generating Neural Cells |
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91 | (28) |
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5.1 Generating neural cells |
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91 | (1) |
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5.2 Neurogenesis in Drosophila |
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92 | (4) |
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Proneural genes promote neural commitment |
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92 | (2) |
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Lateral inhibition: Notch signalling inhibits commitment |
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94 | (2) |
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5.3 Neurogenesis in vertebrates |
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96 | (3) |
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Proneural genes are conserved |
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96 | (1) |
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In the vertebrate CNS, neurogenesis involves radial glial cells |
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96 | (2) |
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Proneural factors and Notch signalling in the vertebrate CNS |
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98 | (1) |
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5.4 The regulation of neuronal subtype identity |
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99 | (3) |
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Neural precursors already have intrinsic identity |
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99 | (1) |
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Different proneural genes - different programmes of neurogenesis |
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100 | (1) |
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Combinatorial control by transcription factors creates neuronal diversity |
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100 | (2) |
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5.5 The regulation of cell proliferation during neurogenesis |
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102 | (7) |
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Signals that promote proliferation |
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102 | (1) |
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Cell division patterns during neurogenesis |
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103 | (1) |
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Asymmetric cell division in Drosophila requires Numb |
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103 | (3) |
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Control of asymmetric cell division in vertebrate neurogenesis |
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106 | (1) |
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In vertebrates, division pattern are regulated to generate vast numbers of neurons |
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107 | (2) |
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5.6 Temporal regulation of neural identity |
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109 | (8) |
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A neural cell's time of birth is important for neural identity |
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109 | (1) |
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Time of birth can generate spatial patterns of neurons |
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110 | (2) |
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How does birth date influence a neuron's fate? |
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112 | (1) |
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Intrinsic mechanism of temporal control in Drosophila neuroblasts |
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112 | (2) |
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Birth date, lamination and competence in the mammalian cortex |
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114 | (3) |
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5.7 Why do we need to know about neurogenesis? |
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117 | (1) |
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117 | (2) |
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119 | (26) |
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6.1 Many neurons migrate long distances during formation of the nervous system |
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119 | (1) |
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6.2 How can neuronal migration be observed? |
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119 | (6) |
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Watching neurons move in living embryos |
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119 | (2) |
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Observing migrating neurons in cultured tissues |
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121 | (1) |
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Tracking cell migration by indirect methods |
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122 | (3) |
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6.3 Major modes of migration |
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125 | (5) |
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Some migrating neurons are guided by a scaffold |
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125 | (1) |
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Some neurons migrate in groups |
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126 | (2) |
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Some neurons migrate individually |
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128 | (2) |
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6.4 Initiation of migration |
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130 | (2) |
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Initiation of neural crest cell migration |
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130 | (1) |
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Initiation of neuronal migration |
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131 | (1) |
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6.5 How are migrating cells guided to their destinations? |
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132 | (5) |
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Directional migration of neurons in C. elegans |
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132 | (1) |
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Guidance of neural crest cell migration |
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133 | (2) |
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Guidance of neural precursors in the developing lateral line of zebrafish |
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135 | (1) |
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Guidance by radial glial fibres |
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136 | (1) |
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137 | (1) |
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6.7 Journey's end - termination of migration |
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138 | (3) |
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6.8 The mechanisms that govern migration of important populations of cortical neurons remain unknown |
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141 | (2) |
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143 | (2) |
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7 How Neurons Develop Their Shapes |
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145 | (20) |
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7.1 Neurons form two specialized types of outgrowth |
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145 | (3) |
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145 | (2) |
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The cytoskeleton in mature axons and dendrites |
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147 | (1) |
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148 | (2) |
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A neurite extends by growth at its tip |
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148 | (1) |
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Mechanisms of growth cone dynamics |
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149 | (1) |
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7.3 Stages of neurite outgrowth |
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150 | (1) |
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Neurite outgrowth in cultured hippocampal neurons |
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150 | (1) |
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Neurite outgrowth in vivo |
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151 | (1) |
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7.4 Neurite outgrowth is influenced by a neuron's surroundings |
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151 | (2) |
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The importance of extracellular cues |
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151 | (1) |
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Extracellular signals that promote or inhibit neurite outgrowth |
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152 | (1) |
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7.5 Molecular responses in the growth cone |
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153 | (4) |
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Key intracellular signal transduction events |
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153 | (1) |
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Small G proteins are critical regulators of neurite growth |
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154 | (1) |
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Effector molecules directly influence actin filament dynamics |
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155 | (1) |
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Regulation of other processes in the extending neurite |
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156 | (1) |
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7.6 Active transport along the axon is important for outgrowth |
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157 | (1) |
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7.7 The development of neuronal polarity |
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158 | (3) |
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Signalling during axon specification |
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158 | (2) |
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Ensuring there is just one axon |
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160 | (1) |
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Which neurite becomes the axon? |
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160 | (1) |
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161 | (3) |
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Regulation of dendrite branching |
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161 | (1) |
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Dendrite branches undergo self-avoidance |
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162 | (1) |
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Dendrites and other sensory structures based on modified cilia |
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163 | (1) |
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164 | (1) |
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165 | (26) |
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8.1 Many axons navigate long and complex routes |
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165 | (1) |
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165 | (1) |
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8.3 How might axons be guided to their targets? |
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166 | (2) |
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8.4 Breaking the journey - intermediate targets |
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168 | (1) |
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169 | (4) |
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Contact guidance in action: pioneers and followers, fasciculation and defasciculation |
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170 | (1) |
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Extracellular matrix provides a substrate for navigating axons |
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170 | (1) |
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Ephs and ephrins: versatile cell surface molecules with roles in contact guidance |
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171 | (2) |
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8.6 Guidance of axons by diffusible cues - chemotropism |
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173 | (4) |
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Netrin - a chemotropic cue expressed at the ventral midline |
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174 | (1) |
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174 | (1) |
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174 | (3) |
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Other axon guidance molecules |
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177 | (1) |
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8.7 How do axons change their behaviour at choice points? |
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177 | (6) |
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Commissural axons lose their attraction to netrin once they have crossed the floor plate |
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177 | (3) |
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Putting it all together - guidance cues and their receptors choreograph commissural axon pathfinding at the ventral midline |
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180 | (3) |
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After crossing the midline, commissural axons project towards the brain |
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183 | (1) |
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8.8 How can such a small number of cues guide such a large number of axons? |
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183 | (2) |
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The same guidance cues are deployed in multiple axon pathways |
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184 | (1) |
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Interactions between guidance cues and their receptors can be altered by co-factors |
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185 | (1) |
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8.9 Some axons form specific connections over very short distances, likely using different mechanisms |
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185 | (1) |
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8.10 The growth cone has autonomy in its ability to respond to guidance cues |
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186 | (1) |
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Growth cones can still navigate when severed from their cell bodies |
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186 | (1) |
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Local translation in growth cones |
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186 | (1) |
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8.11 Transcription factors regulate axon guidance decisions |
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187 | (2) |
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189 | (2) |
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191 | (26) |
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191 | (1) |
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191 | (5) |
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192 | (3) |
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195 | (1) |
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9.3 Principles of map formation |
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196 | (2) |
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Axon order during development |
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196 | (1) |
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Theories of map formation |
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197 | (1) |
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9.4 Development of coarse maps: cortical areas |
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198 | (2) |
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198 | (2) |
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Spatial position of cortical areas |
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200 | (1) |
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9.5 Development of fine maps: topographic |
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200 | (5) |
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200 | (1) |
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Sperry and the chemoaffinity hypothesis |
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201 | (1) |
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Ephrins act as molecular postcodes in the chick tectum |
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202 | (3) |
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9.6 Inputs from multiple structures: when maps collide |
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205 | (6) |
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From retina to cortex in mammals |
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206 | (1) |
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Activity-dependent eye specific segregation: a role for retinal waves |
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207 | (2) |
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Formation of ocular dominance bands |
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209 | (1) |
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Ocular dominance bands form by directed ingrowth of thalamocortical axons |
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210 | (1) |
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Activity and the formation of ocular dominance bands |
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210 | (1) |
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9.7 Development of feature maps |
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211 | (3) |
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Feature maps in the visual system |
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211 | (2) |
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Role of experience in orientation and direction map formation |
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213 | (1) |
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214 | (3) |
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10 Maturation of Functional Properties |
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217 | (26) |
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10.1 Neurons are excitable cells |
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218 | (2) |
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What makes a cell excitable? |
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218 | (1) |
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Electrical properties of neurons |
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218 | (1) |
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219 | (1) |
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10.2 Neuronal excitability during development |
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220 | (5) |
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Neuronal excitability changes dramatically during development |
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221 | (1) |
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Early action potentials are driven by Ca2+, not Na+ |
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221 | (2) |
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Neurotransmitter receptors regulate excitability prior to synapse formation |
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223 | (1) |
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GABAergic receptor activation switches from being excitatory to inhibitory |
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223 | (2) |
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10.3 Developmental processes regulated by neuronal excitability |
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225 | (2) |
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Electrical excitability regulates neuronal proliferation and migration |
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225 | (1) |
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Neuronal activity and axon guidance |
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226 | (1) |
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227 | (8) |
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227 | (1) |
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227 | (2) |
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Synaptic specification and induction |
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229 | (4) |
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233 | (1) |
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Synapse selection: stabilization and withdrawal |
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234 | (1) |
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235 | (6) |
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237 | (1) |
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238 | (1) |
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Mouse models of spinogenesis: the weaver mutant |
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239 | (1) |
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Molecular regulators of spine development |
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239 | (2) |
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241 | (2) |
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11 Life and Death in the Developing Nervous System |
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243 | (24) |
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11.1 The frequency and function of cell death during normal development |
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243 | (2) |
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11.2 Cells die in one of two main ways: apoptosis or necrosis |
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245 | (2) |
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11.3 Studies in invertebrates have taught us much about how cells kill themselves |
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247 | (3) |
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249 | (1) |
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249 | (1) |
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250 | (1) |
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11.4 Most of the genes that regulate programmed cell death in C. elegans are conserved in vertebrates |
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250 | (2) |
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11.5 Examples of neurodevelopmental processes in which programmed cell death plays a prominent role |
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252 | (9) |
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Programmed cell death in early progenitor cell populations |
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252 | (1) |
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Programmed cell death contributes to sexual differences in the nervous system |
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253 | (2) |
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Programmed cell death removes cells with transient functions once their task is done |
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255 | (4) |
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Programmed cell death matches the numbers of cells in interacting neural tissues |
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259 | (2) |
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11.6 Neurotrophic factors are important regulators of cell survival and death |
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261 | (4) |
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261 | (2) |
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263 | (2) |
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11.7 A role for electrical activity in regulating programmed cell death |
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265 | (1) |
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265 | (2) |
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12 Experience-Dependent Development |
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267 | (32) |
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12.1 Effects of experience on visual system development |
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268 | (11) |
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Seeing one world with two eyes: ocular dominance of cortical cells |
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268 | (1) |
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Visual experience regulates ocular dominance |
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269 | (1) |
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Competition regulates experience-dependent plasticity: the effects of dark-rearing and strabismus |
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270 | (2) |
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Physiological changes in ocular dominance prior to anatomical changes |
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272 | (3) |
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Cooperative binocular interactions and visual cortex plasticity |
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275 | (1) |
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The timing of developmental plasticity: sensitive or critical periods |
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275 | (2) |
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Multiple sensitive periods in the developing visual system |
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277 | (2) |
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12.2 How does experience change functional connectivity? |
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279 | (13) |
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Electrical properties of dendrites |
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279 | (1) |
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Cellular basis of plasticity: synaptic strengthening and weakening |
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280 | (2) |
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The time-course of changes in synaptic weight in response to monocular deprivation |
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282 | (2) |
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Cellular and molecular mechanisms of LTP/LTD induction |
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284 | (2) |
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Synaptic changes that mediate the expression of LTP/LTD and experience-dependent plasticity |
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286 | (2) |
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288 | (1) |
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Spike-timing dependent plasticity |
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289 | (3) |
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12.3 Cellular basis of plasticity: development of inhibitory networks |
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292 | (2) |
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Inhibition mediates expression of the effects of monocular deprivation |
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292 | (1) |
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Development of inhibitory circuits regulates the time-course of the sensitive period for monocular deprivation |
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292 | (2) |
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12.4 Homeostatic plasticity |
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294 | (1) |
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12.5 Structural plasticity and the role of the extracellular matrix |
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295 | (2) |
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297 | (2) |
| Suggestions for Further Reading |
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299 | (4) |
| Glossary |
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303 | (18) |
| Index |
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321 | |
