Cellular and Molecular Biology of Neuronal Development

A central problem in neurobiology concerns mechanisms that generate the pro­ found diversity and specificity of the nervous system. What is the substance of diversification and specificity at the molecular, cellular, and systems levels? 4 How, for example, do 1011 neurons each form approximately 10 interconnec­ tions, allowing normal physiological function? How does disruption of these processes result in human disease? These proceedings represent the efforts of molecular biologists, embryologists, neurobiologists, and clinicians to approach these issues. in this volume are grouped by subject to present the varieties The chapters of methods used to approach each individual area. Section I deals with embry­ ogenesis and morphogenesis of the nervous system. In Chapter 3, Weston and co-workers describe the use of monoclonal antibodies that recognize specific neuronal epitopes (including specific gangliosides) for the purpose of defining heterogeneity in the neural crest, an important model system. Immunocyto­ chemical analysis reveals the existence of distinct sUbpopulations within the crest at extremely early stages; cells express neuronal or glial binding patterns at the time of migration. Consequently, interactions with the environment may select for predetermined populations. Le Douarin reaches similar conclusions in Chapter 1 by analyzing migratory pathways and developmental potentials in crest of quail-

I. Embryogenesis and Morphogenesis of the Nervous System.- 1 A Model for Cell Line Divergence in the Ontogeny of the Peripheral Nervous System.- 1. Origin of Ganglion Cells in the Peripheral Nervous System.- 2. Development Fate of Neural-Crest and Their Topographic Relationship to the Central Nervous System.- 2.1. Level of the Trunk.- 2.2. Rhombencephalic Level of the Neural Crest.- 3. Developmental Potentials of the Neural Crest.- 4. Developmental Potentials in Ganglia of Neural-Crest Origin.- 4.1. Peripheral Nervous System Ganglia of Neural-Crest Origin.- 4.2 Cranial Sensory Ganglia of Mixed Placodal and Crest Origin.- 5. General Conclusions and Future Perspectives.- References.- 2 Emergence of Neuronal and Glial Cell Lineages in Primate Brain.- 1. Introduction.- 2. Historical Perspective.- 3. Evidence for Early Cellular Divergence.- 4. Heterogeneity of Proliferative Cells.- 5. Fate of Fetal Radial Glial Cells.- 6. Comparison with the Peripheral Nervous System.- 7. Summary.- References.- 3 Heterogeneity in Neural Crest Cell Populations.- 1. Neural Crest Cells Migrate and Differentiate in Response to Environmental Cues.- 2. Environmental Regulations of Neural Crest Development Has a Number of Possible Explanations.- 2.1. Many of the Macromolecular Constituents Encountered by Migrating Crest Cells are Known.- 2.2. The Developmental State of the Cells Responding to Environmental Cues is Unclear.- 3. Cell-Type-Specific Markers, Recognizing Early Phenotypic Expression in Individual Cells, are Needed to Test Alternative Hypotheses Explaining Neural-Crest Development.- 3.1. A Monoclonal Antibody (E/C8) Recognizes an Epitope Characteristic of Neural Cells and Cn be Used to Disclose a Previously Indistinguishable Crest-Cell Subpopulation.- 3.2. Monoclonal Antibodies against Specific Gangliosides Reveal Other Subpopulations with Neuronal and Glial Traits in Crest Cell Cultures.- 4. Cell-Type-Specific Markers May Permit Analysis of the Normal Time and Order of Segregation of Cells with Specific Developmental Restrictions in Neural-Crest Lineage.- References.- 4 The First Growth Cones in the Central Nervous System of the Grasshopper Embryo.- 1. Introduction.- 2. Divergent Choices by the First Growth Cones in the Central Nervous System.- 3. Channel and Spaces.- 4. Growth Cones and Filopodia.- 5. MP1 Filopodia and Landmark Cells.- 6. Transmission-Electron-Microscopic Reconstructions of MP1 Filopodia.- 7. Filopodia Insertion and Induction of Coated Vesicles.- References.- II. Developmental Expression of Neuraonal Phenotypic Characters.- 5 Surface-Bound and Released Neuronal Glycoconjugates.- 1. Introduction.- 2. Surface Glycoconjugates.- 3. Spontaneously Released Proteins.- References.- 6 The Differentiation of Membrane Properties of Spinal Neurons.- 1. Introduction.- 2. Development of the Action Potential.- 3. Development of Electrical Uncoupling.- 4. Development of Neurotransmitter Sensitivity.- 5. Developmental Significance of Changing Membrane Properties.- 6. Roles of RNA and Protein Synthesis in Differentiation of Neuronal-Membrabe Properties.- References.- 7 The Accumulation of Acetylcholine Receptors at Nerve-Muscle Synapses in Culture.- References.- 8 Transmitter Phenotypic Plasticity in Developing and Mature Neurons in Vivo.- 1. Introduction.- 2. Transmitter Plasticity in the Embryo.- 3. Transmitter Plasticity in the Neonate.- 4. Transmitter Plasticity during Maturity.- 5. Other Peptides, Other Populations.- 6. Conclusions and Prospects.- References.- III. Nerve Growth Factor as a Model Growth Factor.- 9 Mechanisms of the Promotion of Neurite Outgrowth by Nerve Growth Factor.- 1. Introduction.- 2. Actions of Nerve Growth Factor on Growth Cones.- 3. Stabilization of Neurites and Effects of Nerve Growth Factor on Microtubules.- 4. Priming Model and Multiple Actions of Nerve Growth Factor.- 5. Conclusions and Possible Relevance Autonomic Dysfunction.- References.- 10 Cultured Sympathetic Neurons in the Study of Nerve Growth Factor Action.- 1. Long-Term Primary Culture of Dissociated Rat Sympathetic Neurons.- 2. Use of 125I-Labeled Nerve Growth Factor to Characterize the Nerve Growth Factor Receptor in Sympathetic Neuron Cultures.- 3. Retrograde Transport of 125I-Labeled Nerve Growth Factor in Rat Sympathetic-Neuron Cultures.- 4. Intracellular Fate of 125I-Labeled Nerve Growth Factor in Primary Neuron Cultures.- 5. Binding of 125I-Labeled Nerve Growth Factor to Cultures of Various Neural Crest and Placode Derivatives.- References.- 11 Guanethidine-Induced Destruction of Sympathetic Neurons: An Autoimmune “Disease” Prevented by Nerve Growth Factor.- 1. Introduction.- 2. Effects of Immunosuppressive Agents on Guanethidine-Induced Neuronal Destruction.- 3. Nature of the Small Cell Infiltrate in Sympathetic Ganglia of Guanthidine Treated Rats.- 4. Immune Reconstitution Experiments.- 5. Value of Guanethidine-Induced Sympathectomy as a Model of Autoimmune Disease of the Nervous System and of Drug-Induced Autoimmune Disease.- References.- 12 Enhanced Dependence of Fetal Mouse Neurons on Trophic Fators after Taxol Exposure in Organotypic Cultures.- 1. Introduction.- 2. Primary Effects of Taxol.- 3. Reversible Blockade of Neutric Outgrowth during Exposure to Taxol.- 4. Enhanced Nerve Growth Factor Dependence of Dorsal Root Ganglion Neurons after Exposure to Taxol.- 5. Enhanced Dorsal Root Ganglion Dependence of Fetal Dorsal Cord Neurons after Exposure to Taxol.- 6. Concluding Remarks.- References.- 13 The Interaction of Nerve Growth Factor with Its Specific Receptors.- 1. Introduction.- 2. Nerve Growth Factor Receptors on Sensory and Sympathetic Neurons.- 3. Nerve Growth Factor Receptors on PC12 Pheochromocytoma Cells.- 4. The Question of Receptor Conversion.- 5. Effects of Lectin and Anti-Nerve Growth Fator Antibody on Nerve Growth Factor Binding.- 6. Characterization of the Molecular Sizes of the Nerve-Growth-Factor Receptor.- References.- IV. New Neuronal Growth Factors.- 14 Multiple Sites for the Regulation of Neurite Outgrowth.- 1. Introduction.- 2. Results.- 2.1. Substrate-Conditioning Factors.- 2.2. Nerve Growth Factors.- 2.3. Intrinsic Factors.- 3. Summary and Discussion.- 3.1. Substrate-Conditioning Fators.- 3.2. Nerve Growth Factors.- 3.3. Intrinsic Factors.- References.- 15 Nerve Growth Factors in Chick and Rat Tissues.- 1. Introduction.- 2. Materials and Methods.- 2.1. Bioassay.- 2.2. Preparation of Affinity-Purified Antibodies to ß-Nerve Growth Factor.- 2.3. Radioimmunoassay.- 2.4. Chromatography of Chick Embryo Extract.- 3. Results and Discussion.- 3.1. ß Nerve Growth Factor and Anti-ß Nerve Growth Factor.- 3.2. Radioimmunoassay of ß Nerve Growth Factor in the Rat Iris.- 3.3. Bioassay and Radioimmunoassay for Nerve Growth Factor in Fractions of Chick Embryo Extract.- References.- 16 Macromolecular Factors Involved in the Regulation of the Survival and Differentiation of Peripheral Sensory and Sympathetic Neurons.- 1. Introduction.- 2. Culture Systems Used for the Characterization and Purification of Neuronal Trophic Factors.- 3. Age-Dependent Changes in the Requirement for Different Survival Factors in Vitro.- 4. Potentiation of the Effect of Survival Factors by Macromolecules Bound to the Culture-Dish Substrate.- 5. Approaches to the Purification and Characterization of New Neurotrophic Factors.- 6. Concluding Remarks.- References.- 17 Trophic and Neurite-Promoting Factors for Cholinergic Neurons.- 1. Introduction.- 1.1. Neuronotrophic Factors.- 1.2. Neurite-Promoting Factors.- 1.3. Test Systems and Methodology.- 1.4. Factors That Address Cholinergic Neurons.- 2. Cholinergic Neurons in the Peripheral Nervous System.- 2.1. “Target”-Derived Ciliary Neuronotrophic Factors.- 2.2. Other Sources of Ciliary Neuronotrophic Factors.- 2.3. Other Agents That Influence Ciliary Ganglionic Neuronal Survival.- 2.4. Neurite-Promoting and Neurite-Inhibiting Factors.- 3. Cholinergic Neurons in the Spinal Cord.- 3.1. 4 Day Chick-Embryo Lumbar Cord Culture System.- 3.2. Trophic and Toxic Agents for Lumber Cord Neurons.- 3.3. In Vivo Model for Regeneration of Spinal Motor Neurons.- 4. Cholinergic Neurons in Brain Tissue.- 4.1. In Vivo Models for maintenance and Repair of Instrinsic Cholinergic Neurons in the Central Nervous System.- 4.2. Septal Cell and Striatal Cell Cultures.- 4.3. Trophic Agents for Septal and Striatal Neurons.- 5. Conclusions and Projections.- References.- V. Molecular Biology of Neural Development and Function.- 18 Expression of Opioid Peptide Genes in Different Species.- 1. Introduction.- 2. Isolation and Characterization of Opioid Peptide Genes.- 2.1. Chromosomal Locations of Opioid Peptide Genes.- 2.2. Detailed Structure of the Human Proenkephalin Gene Methylation Sites and Regulation.- 2.3. Methylation of Specific CPG Sites in DNA from Different Tissues and Relationship to Regulation of Expression.- 3. Comparative Studies of Opioid Peptide Genes.- 3.1. Comparison of Proenkephalin and Yeast Pro-?-factor.- 4. Polyfunctional Proteins.- 5. Impact of Recombinant DNA Approaches on Studies of Neuropeptide Gene Expression.- References.- 19 Isolation and Characterization of DNA Sequences Coding for Mouse and Human ß-Nerve Growth Factor.- 1. Introduction.- 2. Isolation of Complementary DNA Clones That Code for Mouse Pro-ß Nerve Growth Factor.- 2.1. Characteristics of Mouse ß Nerve Growth Factor Complementary DNA.- 2.2. Localization of the Initiation Methionine Codon and Signal Sequence.- 3. Isolation and Characterization of the Human Chromosomal ß Nerve growth Factor Gene.- 4. Comparison of Human and Mouse Pre-pro-ß Nerve Growth Factor Sequences.- 5. Is ß Nerve Growth Factor a Member of the Insulin Gene Family?.- References.- 20 Linkage Analysis in Familial Dysautonomia Using Variations in DNA Sequence in the ß Nerve Growth Factor Gene Region: A Beginning.- 1. Introduction.- 2. Altered ß Nerve Growth Fcator in Dysautonomia.- 2.1. Hypothesis and Clinical Findings.- 2.2. Biochemical and Immunological Studies of Human ß Nerve Growth Factor.- 2.3. Molecular Biological Studies of ß Nerve Growth Fcator.- 3. Linkage Analysis Using Variations in DNA Sequence.- 3.1. Theoretical Considerations.- 3.2. Applications to Dysautonomia.- 4. Preliminary Studies Looking for Varations in DNA Sequence near the ß Nerve Growth Factor.- 4.1. Selection of Families and Establishment of Lymphoblast Lines.- 4.2. Screening for Varations in DNA Sequence.- 4.3. Future Characterization and Identification of Variant Sites.- 5. Use of Information Derived from Linkage Analysis of the ß Nerve Growth Factor Gene and Dysautonomia.- 5.1. If Linkage Does Exist.- 5.2. If Linkage Does Not Exist.- 5.3. Prospects.- References.- VI. Diseases of Development.- 21 Familial Dysautonomia and Other Congenital Sensory and Autonomic Neuropathies.- 1. Introduction.- 2. Familial Dysautonomia.- 2.1. Natural History.- 2.2. Diagnosis.- 3. Other Congenital Sensory Neuropathies.- 3.1. Diagnostic Differences.- 3.2. Summary.- 4. Conclusion.- References.- 22 Developmental Neurobiology of Human Diseases: Familial Dysautonomia and Related Disorders.- References.