Developmental Neurobiology

Developmental Neurobiology......Page 2
Copyright Page......Page 5
Table of Contents......Page 6
Contributors......Page 12
Preface......Page 18
NEURAL INDUCTION, PATTERN FORMATION, AND CELL SPECIFICATION......Page 20
Tissue and Cellular Events Underlying Primary Neurulation......Page 22
Cell Behaviors Generate Tissue Forces in Primary Neurulation......Page 26
Planar-Cell Polarity Pathway and Convergent Extension......Page 27
Further Reading......Page 28
Introduction - Neural Induction as a Complex Process......Page 29
The Timing of Neural Induction......Page 31
Conclusions - Neural Induction Is Not Yet a Solved Problem......Page 33
Further Reading......Page 34
Gradients and Polarity......Page 35
Positional Information......Page 36
Further Reading......Page 38
Shh Is a Morphogen......Page 40
Shaping the Shh Gradient......Page 42
The Shh Response......Page 43
Is Shh Required for Neural Tube Patterning?......Page 44
Small Molecule Inhibitors of Smo......Page 46
Further Reading......Page 47
Shh Patterning of the Neural Tube......Page 48
Graded Shh Controls Class I and Class II Protein Expression......Page 50
Additional Signals Involved in Dorsoventral Patterning of the Neural Tube......Page 52
Hedgehog-Binding Proteins and Feedback Loops......Page 53
Gli Proteins and Dorsoventral Patterning......Page 55
Relevant Website......Page 57
Canonical Pathway - Wnt Receptors and Alternative Ligands......Page 58
Canonical Pathway - Events in the Cytosol......Page 59
Wnt Signaling in Synapse Development - Divergent Pathways and Diverse Mechanisms......Page 60
Summary......Page 62
Further Reading......Page 63
Evolutionary Conservation of BMP Inhibition during Neural Induction......Page 64
Opposing Graded BMP and Hh Signals Pattern the Vertebrate Neuroectoderm......Page 65
Graded BMP-Mediated Repression of Neural Genes in Drosophila......Page 67
Neural Patterning in Other Groups of Organisms......Page 69
DV Inversion in Vertebrates?......Page 71
Relevant Websites......Page 73
Spatiotemporal Aspects of RA Signaling in Early Mouse Embryos......Page 74
Role of RA in Hindbrain Anteroposterior Patterning......Page 75
Role of RA in Spinal Cord Dorsoventral Patterning......Page 76
RA Antagonism of Fgf8 Expression in the Primitive Streak Controls Posterior Patterning......Page 77
Further Reading......Page 78
Hox Gene Function......Page 80
FGF Regulates Hox Expression......Page 83
Regulation of Hox Genes by Transcription Factors......Page 84
Hox Cofactors......Page 86
Competition and Sharing......Page 87
Global Regulatory Elements......Page 88
Further Reading......Page 89
Relevant Websites......Page 90
Classical Studies on Motor Neuron Development in the Chick......Page 91
Positional Information and Cell Type Specification in the Spinal Cord......Page 92
Establishing Patterns of Hox Gene Expression along the Rostrocaudal Axis......Page 93
Hox Proteins Function in the Specification of Segmentally Restricted Motor Columns......Page 94
Identification of Motor Pools at Early Stages by Transcription Factor Expression......Page 95
Hox Proteins and the Intrasegmental Diversification of Motor Pool Identities......Page 96
Conclusions......Page 97
Further Reading......Page 98
Positioning of the Brain Primordia......Page 99
Function of Local Organizers......Page 101
First Step in Competence: Integration of the Signal by the Surrounding Tissue......Page 102
A Further Aspect of Competence: Predetermination of Cellular Fate......Page 103
Functional Range of Organizers Is Determined by the Receiving Field......Page 104
Further Reading......Page 105
Establishment of the Isthmic Organizer......Page 106
The Forebrain-Midbrain Junction......Page 107
Interactions among Midbrain Organizers......Page 108
Midbrain Arcs......Page 109
Nuclei Not of Midbrain Origin......Page 110
Optic Tectum......Page 111
Midbrain Patterning and Invertebrates......Page 112
Further Reading......Page 113
Why We Use Models......Page 114
Columnar Models......Page 115
Further Reading......Page 117
Key Features of Early Forebrain Development......Page 119
Hypothalamus......Page 120
Eye......Page 121
Diencephalon......Page 122
Further Reading......Page 123
Nonneural Organizers of the Neural Plate......Page 124
Forebrain specification......Page 125
Role in roof plate induction......Page 126
Hypothalamic morphogenesis and induction......Page 127
Expression of Bmps and Wnts......Page 128
Shh signaling at the ventral midline......Page 129
Bmp signaling at the ventral and dorsal midlines......Page 130
Evidence for a positive feedback loop......Page 131
Zic2  Roof Plate Pathway in the Dorsal Midline......Page 132
Future Directions......Page 133
Further Reading......Page 134
Putting the Neocortex in Its Place......Page 135
Areas Differentiate within a 'Uniform' Cortical Plate Characterized by Exuberant Distribution of Projection Neurons......Page 136
Cytoarchitecture and Exuberant Projection Neurons......Page 137
Roles for Morphogens and Transcription Factors in Control of Area Identity......Page 138
Sp8......Page 139
Wnts and BMPs......Page 140
Translation of Graded Expression of TFs by Cortical Progenitors and Their CP Progeny into Sharp Borders Exhibited by Cortical........Page 141
What Is 'Area Identity'?......Page 142
Further Reading......Page 143
Retinal Patterning along the A-P Axis......Page 144
Retinal Patterning along the D-V Axis at the Early Stages......Page 146
Retinal Patterning along the D-V Axis at the Later Stages......Page 147
Other Aspects of Retinal Patterning......Page 148
Further Reading......Page 149
Lateral Inhibition and Selection of a Cell within a Proneural Cluster......Page 150
Cis-Regulatory Logic of E(Spl) Expression in a PNC......Page 152
Biasing the Outcome of Notch Signaling......Page 154
Biasing Binary Cell Fate Decisions in the SOP Lineage......Page 155
Notch Signaling in Vertebrate Neurogenesis......Page 157
Further Reading......Page 158
Notch Receptors and DSL Ligands......Page 159
Regulation of DSL Ligand Activity......Page 160
DSL endocytosis is required for Notch activation......Page 161
DSL endocytosis promotes physical dissociation of Notch......Page 163
Endocytosis and Trafficking Regulate Notch Levels and Activity......Page 164
DSL-Independent Endocytosis and Trafficking of Notch......Page 165
Notch Target Genes Regulated by CSL......Page 166
Elaborations on Notch Signaling, Both Canonical and Noncanonical......Page 167
Further Reading......Page 168
Neuronal Differentiation......Page 169
Neurons versus Glia......Page 171
Neuronal Subtype Specification......Page 172
Concluding Remarks......Page 173
Further Reading......Page 174
Regulation of Hes Gene Expression......Page 175
Hes Expression in the Developing Nervous System......Page 177
Hes Genes Regulate Maintenance of Neural Stem Cells......Page 179
Hes Genes Regulate Boundary Formation......Page 181
Summary......Page 182
Further Reading......Page 183
Role of SOX Factors in Defining Neural Competence......Page 184
Role of SOX Factors in the Maintenance of Identity and Differentiation of Neural Progenitor Cells of the Central Nervous System......Page 185
Role of SOX Factors in the Maintenance and Differentiation of Neural Progenitor Cells of the Peripheral Nervous System......Page 187
Further Reading......Page 189
D/V Patterning of the Spinal Cord......Page 191
Negative Gene Regulation: Cross-Repression and Derepression......Page 192
Cell Specification Factors Downstream of Progenitor Factors......Page 193
LIM Networks in Postmitotic Neurons......Page 194
R/C patterning, Hox Genes, and Motor Pools......Page 195
Further Reading......Page 196
Histone Modification......Page 197
Other Chromatin Remodeling Mechanisms......Page 198
Endogenous Signaling Pathways......Page 199
Invasive DNA......Page 200
Further Reading......Page 201
Motor Neuron Progenitors: Extrinsic Signals......Page 203
Stepwise Progression in Motor Neuron Diversification......Page 204
The LIM Code and Motor Neuron Diversification......Page 206
The Molecular Underpinnings of the LIM Factors......Page 207
Motor Neuron Soma Migration......Page 208
Locomotor Circuitry: Dendrite Patterning and Synaptogenesis......Page 209
Further Reading......Page 210
Human Genetic Malformations......Page 211
Neuronal Migration......Page 212
Molecular Pathways of Neuronal Migration......Page 213
LIS: Clinical Aspects and Molecular Genetics......Page 214
Further Reading......Page 216
Relevant Website......Page 217
Microarrays......Page 218
Voxelation......Page 219
Gene Expression Nervous System Atlas......Page 220
SymAtlas......Page 221
Molecular Relationships within the Mammalian Brain......Page 222
Further Reading......Page 224
NRSE/RE1: The DNA Binding Element of REST/NRSF......Page 225
REST/NRSF in Development......Page 226
Regulation of REST/NRSF......Page 227
REST/NRSF and Cancer......Page 228
REST/NRSF-Mediated Transcriptional Repression and Silencing......Page 229
REST/NRSF as an Activator......Page 230
Further Reading......Page 231
Genetic Mechanisms of Apterous Neuron Specification......Page 232
The Apterous Cluster Is Generated by the Stem Cell Neuroblast 5-6T......Page 233
Important Themes during Neuronal Subtype Specification......Page 234
Conclusion......Page 235
Further Reading......Page 236
Radial Glia Are Neural Stem Cells......Page 237
Gliogenesis in the Adult Central Nervous System......Page 238
Further Reading......Page 239
Extrinsic Factors in Mesencephalic DA Neuron Development......Page 240
Intrinsic Factors in Mesencephalic DA Neuron Development......Page 241
The Control of DA Axonal Development......Page 242
Conclusion......Page 243
Further Reading......Page 244
Neuronal Cell Types of the OE and VNO......Page 245
Two Phases of Olfactory Neurogenesis......Page 247
Intrinsic Factors: Transcription Factors Regulating Mitotic Cell Populations......Page 248
Fibroblast Growth Factors......Page 251
Growth and differentiation factor 11 and feedback inhibition of neurogenesis......Page 253
Summary and Conclusions......Page 254
Further Reading......Page 256
Spatial Control of OPC Generation by Signals from the Ventral and Dorsal Midline......Page 257
OPC Generation in the Forebrain......Page 258
Role of Transcription Factors in OPC Development: The OLIG Genes......Page 259
Control of OPC Proliferation......Page 260
OPCs in the Adult CNS......Page 261
Further Reading......Page 262
Role of Notch Signaling in Prosensory Specification......Page 264
Pax2, Gata-3, and Lfng......Page 265
Commitment of Hair Cells......Page 266
Differentiation and Survival of Hair Cells......Page 267
Role of TH Signaling in Hair Cell Differentiation......Page 268
Further Reading......Page 269
Oriented Cell Divisions......Page 270
Molecular Regulation of Retinal Cell Proliferation......Page 271
Competency Model for Retinogenesis......Page 272
Modes of Migration......Page 273
Coordination of Differentiation......Page 274
Protein Trafficking and Cellular Differentiation......Page 275
Conclusions......Page 276
Further Reading......Page 277
Coordinating Cell Fate and Proliferation......Page 278
Environmental Factors in Retinal Cell Fate Decisions......Page 279
bHLH and Homeodomain Transcription Factors......Page 280
Ganglion cells......Page 281
Asymmetric Cell Divisions in Retinal Cell Fate Decisions......Page 282
Further Reading......Page 283
Retinal Progenitors in Normal Development......Page 285
Retinal Stem Cells in the Ciliary Marginal Zone......Page 286
The Ciliary Epithelium......Page 287
Intrinsic Stem Cells, Rod Precursors, and Muumlller Glia......Page 288
Further Reading......Page 289
Induction and EMT......Page 290
Cranial Neural Crest......Page 293
Enteric Nervous System......Page 296
Trunk Neural Crest......Page 297
Ventral Pathway......Page 298
Plasticity of Trunk Neural Crest Cells......Page 299
Further Reading......Page 300
Markers of Schwann Cell Development......Page 301
beta-Neuregulin-1 and the Neural Crest......Page 303
beta-Neuregulin-1 and Schwann Cell Precursors......Page 305
Notch and Schwann Cell Precursors......Page 306
Trophic Support of Neuronal Survival......Page 307
Radial Sorting......Page 308
Myelin-Related Transcription Factors......Page 309
Further Reading......Page 310
Axon Signals Sustaining Schwann Cell Precursors......Page 312
Myelination......Page 313
Axon Dependence on Schwann Cells......Page 315
Further Reading......Page 316
Components of the NRG-E rbB Signaling System......Page 317
NRG1-ErbB Signaling Regulates SC Lineage Development......Page 318
NRG1-ErbB Signaling as a Master Regulator of Myelination in the Peripheral Nervous System......Page 319
ErbB Signaling in the Mature Peripheral Nervous System and in Pathological Conditions......Page 322
Future Research......Page 323
Further Reading......Page 324
Hooked on Neuregulins: The Schwann Cell Precursor......Page 325
Choosing between Two Alternative Fates during Terminal Differentiation......Page 326
Escorting Schwann Cells into the Myelinating Stage......Page 327
Regulating Myelin Gene Expression......Page 328
Further Reading......Page 329
Development of Melanocytes......Page 331
Melanoblast Specification: The Interplay between Signaling Pathways and Transcription Regulation......Page 332
Melanoblast Specification: Cell Number and Location......Page 335
Melanoblast Survival, Proliferation, and Migration......Page 336
Adult Melanocyte Stem Cells......Page 337
Further Reading......Page 338
Relevant Website......Page 339
Origin of the Autonomic Nervous System from the Neural Crest......Page 340
Molecular Control of Migration......Page 341
Gangliogenesis......Page 342
Sympathetic Ganglia: Neuronal Differentiation and Connections......Page 343
Parasympathetic Ganglia: Neuronal Differentiation and Connections......Page 347
Enteric Ganglia: Neuronal Differentiation and Connections......Page 349
Further Reading......Page 350
Autonomic Gangliogenesis......Page 352
Neuronal Survival: The Neurotrophic Hypothesis......Page 355
Regulation of Target Innervation......Page 356
Neurochemical Plasticity......Page 357
Further Reading......Page 358
ENS Control of Motile and Secretory Behaviors......Page 360
Serotonin Is Important in the Normal and Abnormal Behavior of the Bowel......Page 361
Enteric Neurons and Glia Develop from a Multipotent Precursor Population......Page 363
Development of the ENS Is a Progression of Interacting Cell Autologous and Nonautologous Events......Page 364
Subtle ENS Defects May Arise as a Result of Mutations in Genes Required Late in ENS Development......Page 365
Further Reading......Page 366
Sexual Differentiation of the CNS......Page 367
Sexual Differentiation in Adulthood......Page 369
Sexual Differentiation of the Human Brain and Behavior......Page 370
Further Reading......Page 372
Major Principles and Model Systems......Page 373
Axon guidance......Page 376
The Role of Receptors for Estrogen and Testosterone......Page 378
Further Reading......Page 379
AXON GUIDANCE AND SYNAPTOGENESIS......Page 382
The Chemoaffinity Hypothesis......Page 384
Multiple Phases in the Development of a Topographic Map......Page 385
DV Mapping......Page 387
Further Reading......Page 389
Historical Perspective......Page 391
Nasal-Temporal Mapping in the Retinotectal Projection......Page 392
Dorsal-Ventral Mapping in the Retinotectal Projection......Page 395
Guidance Cue Gradients in Other Topographic Maps......Page 396
Correlated RGC Firing Is Required for Topographic Map Refinement......Page 397
Postsynaptic NMDA Receptors Induce Map Refinement by Eliminating Inappropriate Connections......Page 398
Further Reading......Page 399
The Growth Cone......Page 400
Axon Extension and Branching......Page 401
Gradient guidance......Page 402
Contact-mediated guidance......Page 403
Guidance Cue Patterning......Page 404
Further Reading......Page 405
Guidepost Cells and Guidance Cues in Axon Guidance......Page 406
Attracting to the Midline......Page 407
Adhesion at the Midline......Page 408
Subplate Neurons as Guidepost in the Maturation of Visual Cortical Circuit......Page 409
Further Reading......Page 410
General Definition of Cell Adhesion Molecules......Page 412
Immunoglobulin Superfamily......Page 413
Semaphorins and neuropilins......Page 414
Rhombomeres of the hindbrain......Page 415
Genetic control of the midline in......Page 416
The floor plate of the vertebrate neural tube......Page 417
Tnc Is a Multimodular and Multifunctional ECM Component......Page 418
CSPGs and KSPGs of the central nervous system......Page 419
Receptor protein tyrosine phosphatases in neuron-glia interactions......Page 420
Further Reading......Page 421
CS Neuron Differentiation......Page 422
Decussation and Midline Crossing......Page 423
Topographic Refinement of CS Terminations in the Spinal Gray Matter......Page 424
Activity-Dependent Refinement of CS Axon Terminal Connections......Page 427
Development of CS Control of Skilled Motor Behavior......Page 429
Development of the Cortical Motor Map......Page 431
Conclusion and Implications for Rehabilitation......Page 432
Further Reading......Page 433
Crossing or not crossing at the optic chiasm......Page 434
Topographic mapping in the optic tectum/superior colliculus......Page 435
Innervating and mapping in the visual cortex......Page 436
Formation of an Olfactory Sensory Map in the Olfactory Bulb......Page 437
From the Olfactory Bulb to Higher Olfactory Centers......Page 438
Peripheral Growth and Projection of Somatic Sensory Neurons Are Guided by Neurotrophins and Semaphorins......Page 439
Further Reading......Page 440
Growth Cone Steering......Page 441
Guidance Cues and Their Receptors......Page 443
Further Reading......Page 445
Organization of the Optic Pathway......Page 446
Fiber Organization in the Optic Nerve, Chiasm, and Tract......Page 447
Decussation Decisions at the Optic Chiasm......Page 448
Target Innervation......Page 449
Genetic Mutations in Pigment-Related Genes Reduce Binocular Vision by Reallocating Retinal Fibers at the Optic Chiasm......Page 450
Further Reading......Page 451
Sources of Activity in the Developing Visual System......Page 452
Eye-Specific Maps in the Lateral Geniculate Nucleus......Page 453
Ocular Dominance Column Formation and Plasticity......Page 454
Molecular Mechanisms of Plasticity......Page 455
Further Reading......Page 456
NMDARs in Early Brain Development......Page 457
Differentiation......Page 458
Competition and Segregation - Visual Pathways......Page 459
Competition and Segregation - Somatosensory Pathways......Page 462
Structural Refinement - Synapses......Page 463
Refinement of receptive fields and response properties......Page 465
A Developing NMDA Receptor Complex......Page 466
Further Reading......Page 467
Cytoarchitecture......Page 468
Development of Tectum and Axonal Guidance......Page 472
Behavioral Correlates......Page 473
Further Reading......Page 474
Features of Nascent and Mature Synapses......Page 475
Process of Dendritic Arbor Development......Page 476
Conclusion......Page 477
Further Reading......Page 478
Shh as a Chemoattractant for Commissural Neurons......Page 479
Shh as a Chemorepellant for Postcrossing Commissural Neurons......Page 480
Wnt5 in Drosophila......Page 481
Wnts in the Nematode......Page 482
Further Reading......Page 483
Shh Is a Chemoattractant for Commissural Axons......Page 484
Boc Is a Receptor for Shh in the Guidance of Commissural Axons to the Floor Plate......Page 486
Shh Guides Commissural Axons along the.Longitudinal Axis of the Spinal Cord......Page 487
Shh Is a Negative Regulator of Retinal Ganglion Cell.Axon Growth......Page 488
Molecular Mechanism underlying Shh-.Mediated Axon Guidance......Page 489
Further Reading......Page 490
Netrin Structure......Page 491
Chemoattractant Signaling in Response to Netrin-1......Page 493
Regulating Growth Cone Response to Netrin-1......Page 495
Other Potential Netrin Receptors......Page 496
Conclusion......Page 497
Further Reading......Page 498
Adhesive Contacts of Growth Cones......Page 499
Cadherins and IgCAMs......Page 501
Laminins......Page 502
Integrins......Page 503
Adhesion Molecules and Axonal Regeneration......Page 504
Further Reading......Page 505
Postsynaptic Scaffolding Proteins......Page 506
Principles Governing Postsynaptic Differentiation......Page 507
Induction of Postsynaptic Differentiation......Page 508
Synaptic Adhesion Molecules......Page 509
Postsynaptic Receptors......Page 510
F-Actin......Page 511
Further Reading......Page 512
Excitatory Synapses: Postsynaptic Organization......Page 514
The PSD-95 Family and Other Major PSD Scaffold Proteins......Page 515
Signaling Proteins......Page 517
Inhibitory Synapses: Postsynaptic Organization......Page 518
Synapse Development: A Morphological View......Page 519
Further Reading......Page 520
Presynaptic Development: Initial Events......Page 521
Maturation of Nascent Presynaptic Sites......Page 523
Cellular Mechanisms of Presynaptic Differentiation......Page 525
Molecular Mechanisms of Presynaptic Differentiation......Page 526
Further Reading......Page 529
Multiple Stages of Synapse Assembly......Page 531
Role of Synaptic Cell Adhesion Molecules in Synapse Assembly......Page 533
Stabilization of Synapses......Page 535
Functional Maturation of Presynaptic Terminals and the Role of Activity......Page 536
Further Reading......Page 537
The Motor Neurons and Their Projections......Page 539
The Decision to Defasciculate......Page 541
Molecular Recognition of Synaptic Targets......Page 542
Early Roles for Activity at the Neuromuscular Junction......Page 543
The Roles of Activity in Neuromuscular Junction Growth and Function......Page 544
Transsynaptic Signals Involved in Neuromuscular Junction Development......Page 545
Further Reading......Page 546
Relevant Websites......Page 547
Kinetics of Primary and Secondary Myotube Formation......Page 548
AChR Accumulation......Page 549
AChR aggregation......Page 550
Maturation of the Nerve Terminal......Page 551
Formation of the folds......Page 552
Changes in AChR expression......Page 553
Accumulation of Myonuclei......Page 554
Development of Muscle Fiber Homogeneity......Page 555
Further Reading......Page 556
Collagen IV......Page 557
Laminins......Page 558
Heparan Sulfate Proteoglycans......Page 559
Dystroglycan Complex......Page 560
Cadherins......Page 561
Further Reading......Page 562
The Vertebrate Neuromuscular Junction: An Excellent System for Studying Neurotransmitter Receptor Accumulation in the Postsynap......Page 563
Expression of AChRs throughout Uninnervated Differentiating Myotubes Is Replaced by Synapse-Specific Expression in Innervated Fibers......Page 564
Candidate Nerve-Derived Factors Inducing AChR Gene Transcription......Page 565
Essential functions of NRG1 in neuromuscular development......Page 566
In vivo genetic studies of AGRIN'S roles in synapse-specific gene expression......Page 567
A number of proteins in addition to AChRs and MUSK display synapse-specific expression......Page 569
Myocentric Model......Page 570
Further Reading......Page 571
From pi to µ......Page 572
Is competition local?......Page 574
Are There Intrinsic Hierarchies Among Motor Neurons?......Page 575
Neurotrophic Influences on the Rate of Synapse Elimination......Page 576
Synapse Elimination and Neurodegenerative Disease......Page 577
Summary......Page 578
Further Reading......Page 579
The General Characteristics of Perisynaptic Schwann Cells at the Neuromuscular Junction......Page 580
Role of PSCs in Synaptogenesis......Page 582
Remodeling......Page 583
Degeneration and Regeneration......Page 584
Further Reading......Page 585
Glia Induce Synapses in Multiple Neuron Classes......Page 586
Contact-Mediated Synaptogenesis......Page 587
Glia Influence Synapse Elimination......Page 588
Glia Influence Synaptic Structure, Stability and Location......Page 589
Conclusions......Page 590
Further Reading......Page 591
The Excitatory/Inhibitory Shift of GABA Actions during Development......Page 592
How Does the E-to-I Shift Occur?......Page 593
GABAergic Synapses Are Formed before Glutamatergic Synapses......Page 594
Giant Depolarizing Potentials: A.Primitive Network Oscillation, Present in All Developing Systems, That Disappears When the E-to-I Shift Is Completed......Page 596
Developmental Curve of Primate Neurons......Page 597
I-to-E Shift after Insults: Pathogenesis Recapitulates Ontogenesis......Page 598
Implications of These Basic Rules and a General Model of the Establishment of Activity in Developing Cortical Networks......Page 599
Further Reading......Page 600
NEUROGENESIS, NEUROTROPHISM, AND REGENERATION......Page 602
Introduction......Page 604
Temporal Determinants: Birthdate and Laminar Fate......Page 605
Asymmetric and Symmetric Division of Cortical Progenitors Function in the Generation of Cortical Cell Diversity......Page 606
Does the Segregation of Progenitors to the Ventricular Zone and Subventricular Zone Represent a Bifurcation of Cell Fates?......Page 607
Intrinsic Factors of Cortical Cell-Fate Specification......Page 608
Further Reading......Page 609
Cell Cycle and Cell Fate in the Drosophila Nervous System......Page 611
Cell Cycle Genes Regulate Cell Fate and Differentiation in the Nervous System......Page 612
Cyclin-Dependent Kinase Inhibitors......Page 613
The Retinoblastoma Protein......Page 614
Differentiation and Patterning Factors Regulate the Cell Cycle......Page 615
Conclusions......Page 616
Further Reading......Page 617
The Functions of PCD in the Nervous System......Page 618
Molecular Regulation of Cell Death and Survival by NTFs......Page 619
Intracellular Regulation of Cell Death......Page 620
Different Types of Neuronal Death......Page 622
Pathological Neuronal Death......Page 624
Further Reading......Page 625
Apoptosis in the Nervous System and the Discovery of Neurotrophic Factors......Page 626
Lessons from Mutant Mice......Page 627
Trk Receptors and Ligands Regulate Cell Death In Vivo in the Sympathetic Nervous System......Page 628
Programmed Cell Death in the Parasympathetic Nervous System......Page 630
Mechanisms Governing Neuron Number in the ENS......Page 631
Summary......Page 632
Further Reading......Page 633
Autophagic Cell Death: Origins of the Concept......Page 634
Prevention of Autophagic Cell Death by Pharmacological Inhibitors of Autophagy......Page 635
Autophagy in Neuronal Death......Page 636
Neuronal Autophagy in Acute Neurological Conditions......Page 637
Autophagy in Neurodegenerative Diseases......Page 638
Further Reading......Page 639
Neurotrophin Actions Are Mediated by Distinct Cell Surface Receptors......Page 641
Cell Survival......Page 643
Neurotrophin Pharmacology......Page 644
Clinical Trials with Neurotrophins......Page 645
Further Reading......Page 646
Neurotrophic Factors and Their Receptors in the Gut......Page 647
Neurturin......Page 648
Neurotrophic Factors and Postnatal Changes in the ENS......Page 649
Expression of Neurotrophic Factors and Their Receptors in the Adult Gut......Page 650
Are Neurotrophic Factors Involved in Clinical Conditions Affecting the ENS?......Page 651
Further Reading......Page 652
Schwann Cells......Page 653
Ependymoglia......Page 654
Regulation of Oligodendrocyte and Schwann Cell Differentiation by Glial Growth Factors: Importance for Etiology and Treatment of MS......Page 655
Regulation of Neuronal Differentiation during Development......Page 657
Role of Glia-Derived Growth Factors in Neural Regeneration in the Central Nervous System......Page 658
Further Reading......Page 659
Location of Adult NSCs in the Mammalian Brain......Page 660
Identification of NSCs by Molecular Markers......Page 662
Extracellular Influences......Page 663
Intracellular Signaling......Page 664
Conclusion......Page 665
Further Reading......Page 666
History......Page 667
Adult Hippocampal Neurogenesis......Page 668
Regulation......Page 669
Medical Relevance......Page 670
Further Reading......Page 671
Neural Stem Cells......Page 672
Environmental Cues......Page 673
Stroke......Page 674
Spinal Cord Injury......Page 675
Endogenous Stem Cell Recruitment for CNS Repair......Page 678
Further Reading......Page 679
Characterization of Neural Stem Cells......Page 681
Modulation of Neurogenesis in the Aged Brain......Page 682
Implications of Decreased Neurogenesis in the Aging Brain......Page 683
Further Reading......Page 684
Normal Adult Plasticity......Page 685
Puberty, Reproduction, and Sex Steroids in Synaptic Sprouting......Page 686
Neuronal Sprouting and Aging......Page 687
Further Reading......Page 689
Classical Morphogens with Novel Old Functions......Page 690
Neurotrophins......Page 691
Ephrins......Page 692
Slits......Page 693
Calcium......Page 694
Developmental Guidance Cues in the Adult......Page 695
Intrinsic Regenerative Capacity......Page 697
Further Reading......Page 699
Protecting the Cord from Further Damage......Page 700
Axon growth ability......Page 701
Transplantation of permissive cells......Page 702
Treatments That Enhance Plasticity......Page 703
Prostheses and Other Devices......Page 704
Further Reading......Page 705
Peripheral Nerve Regeneration......Page 706
Neural Repair in the CNS......Page 707
Further Reading......Page 709
Subject Index......Page 710