Foundations Of Neural Development

PROLOGUE: The Rationalist Philosophers All I Know Is That I Know Nothing The Benefits of Having an Immortal Soul What Does All This Philosophy Stuff Have to Do with This Book?

CHAPTER 1. The Metazoans' Dilemma: Cell Differentiation and Neural Induction 1.1. Metazoans Evolved the Ability to Produce Cells with Very Different Functions 1.2. Preformationism Offered an Easy but Wrong Solution, While Epigenesis Seemed Incomprehensible 1.3. The Rediscovery of Genes Set the Stage for Understanding Development 1.4. Gene Expression Directs Cell Differentiation Researchers at Work: Do Differentiating Cells Dispose of Unused Genes? 1.5. Scientists Domesticated a Simple Worm to Address the Questions of Cell Differentiation 1.6. Mitotic Lineage Guides Cell Differentiation in Worms Box 1.1. Kerfuffles in Language: "Cell Fate" and "Commitment" 1.7. Embryonic Development Begins by Forming Three Distinct Germ Layers 1.8. The Vertebrate Nervous System Begins as a Simple Tube 1.9. Many Embryos, Including All Vertebrates, Display "Self-Regulation" 1.10. Self-Regulation Seems Incompatible with Mitotic Lineage-Directed Differentiation 1.11. Experimental Embryology Revealed Inductive Processes Underlying Self-Regulation 1.12. A Region of the Vertebrate Embryo Seems to "Organize" Development Researchers at Work: The Dorsal Lip of the Blastopore Can Organize a New Individual 1.13. Long Abandoned, the Organizer Was Uncovered through Molecular Biological Techniques Researchers at Work: A Gene Is Discovered That Acts as an Organizer 1.14. What Organizes the Organizer? 1.15. In Insects, Epidermal Cells Compete to Become Neuroblasts Summary

CHAPTER 2. Coordinating Fates: Development of a Body Pattern 2.1. Darwin Noted That Vertebrate Embryos Start Off Looking Alike Box 2.1. A Step Too Far 2.2. Mother Knows Best: Maternal Factors Establish a Basic Polarity of the Body Researchers at Work?Two Heads Are Not Better Than One Box 2.2. Meet Drosophila melanogaster, the Well-Segmented Organism 2.3. A Cascade of Gene Regulatory Proteins Organizes a Body Plan 2.4. Some Mutations in Drosophila Transform Body Parts Whole 2.5. Hox Genes Are Crucial for Vertebrate Development, Too 2.6. Hox Genes Direct "Segmentation" in the Mammalian Brain Box 2.3. Kerfuffles in Language: "Segmentation" 2.7. Hindbrain Rhombomere Fates Are Directed by Homeobox Genes 2.8. Several Signals Designate the Caudal End of the Body and Nervous System 2.9. Continued Gradients in BMP Signaling Establish the Dorsal-Ventral Axis in the Nervous System Researchers at Work: What Notochord Factor Induces the Floor Plate and Motor Neurons? 2.10. Find Out Where You Are to Coordinate Your Fate with That of Your Neighbors Summary

CHAPTER 3. Upward Mobility: Neurogenesis and Migration 3.1. The Same Gene May Play a Role in Many Different Developmental Events 3.2. The Developing Brain Generates Neurons at a Tremendous Rate 3.3. Shortly after Division, Neural Cells Diverge to Become Neurons or Glia Researchers at Work: Labeling of Dividing Cells Disputes the Idea That Lineage Determines Fate 3.4. The Cerebellum and Cerebral Cortex Form in Layers 3.5. We Can Label Newly Synthesized DNA to Determine the Birthdates of Cells 3.6. Newborn Cells Shinny Up Glial Poles Researchers at Work: The Cortex Develops in an Inside-Out Manner 3.7. A Few Brain Regions Display Continuing Neurogenesis throughout Life Box 3.1. The Controversy of Neurogenesis in Adulthood 3.8. Neural Crest Cells migrate to Positions throughout the Body 3.9. Cell Adhesion Molecules Attract and Repel Migrating Cells 3.10. Cerebellar Granule Cells Parachute Down from Above Researchers at Work: Weaver Neurons Fail to Grasp Glial Fibers 3.11. Cells Crucial for Smell and Reproduction Migrate into the Embryonic Brain Summary

CHAPTER 4. Seeking Identity: Neural Differentiation 4.1. The Fruit Fly Retina Develops through an Orderly Progression of Gene Expression and Signaling Box 4.1. Transgenics, Knockouts, and Knockins 4.2. Several Factors Influence Whether a Cell Will Become a Neuron or a Glia 4.3. The Molecular Differentiation of Motor Neurons Is Orderly 4.4. Neural Crest Cells Are Affected by Their Migration and Destination Researchers at Work: Neural Crest Cells Adopt New Fates after Transplantation 4.5. The Neurotransmitter Phenotypes of Autonomic Neurons Are Guided by Their Targets Researchers at Work: Targets Can Regulate the Neurotransmitter Phenotype of Afferents 4.6. The Fate of a Cortical Neuron Is Influenced Both Before and After Migration Researchers at Work: Cortical Neuron Fate Is Specified after the S Phase 4.7. Later Events in Development Are More Evolutionarily Labile Summary

CHAPTER 5. Feeling One's Way: Axonal Pathfinding 5.1. Ramón y Cajal Described Growth Cones and Discerned Their Significance 5.2. In Vitro Approaches Reveal Principles of Axonal Growth and Adhesion Researchers at Work: Getting a Grip: The Role of Adhesion in Axonal Growth 5.3. Guidance Cues May Be Attractive to One Type of Growth Cone and Repulsive to Others 5.4. Families of Receptors Offer a Multitude of Guidance Cues 5.5. Pioneer Neurons and Guidepost Cells Establish Pathways for Later Axons 5.6. Many Axonal Growth Cones Have to Deal with Crossing the Midline Researchers at Work: What Makes the Floor Plate so Attractive 5.7. Motor Neuronal Axons Must Find the Correct Target Muscles Researchers at Work: Can You Navigate Your Way Home? 5.8. The Axons of Retinal Ganglion Cells Must Reach the Midbrain Researchers at Work: Rather Walk over Here 5.9. The Corpus Callosum Is Directed across the Midline by a Glial Bridge Researchers at Work: Glia Can Help Axons Cross a Border Summary

CHAPTER 6. Making Connections: Synapse Formation and Maturation 6.1. Calcium Regulators and Environmental Sensors Evolved to Mediate Synaptic Signaling 6.2. We Can Divide Synapse Structure and Development into Three Parts 6.3. A Synapse Begins with Adhesion Researchers at Work: Dendritic Spines Compete for Survival 6.4. Fragile X Syndrome Suggests There Can Be Too Much of a Good Thing 6.5. Pre- and Postsynaptic Partners Tightly Anchor One Another as a Synapse Develops Researchers at Work: Presynaptic and Postsynaptic Receptors Trigger Synaptic Development 6.6. Neuromuscular Junctions Illustrate That Synapse Formation Is a Dance for Two (or More) 6.7. Motor Neuronal Agrin Promotes the Aggregation of Acetylcholine Receptors 6.8. Neuregulins Boost Local AChR Expression in Muscle and Maintain Terminal Schwann Cells 6.9. Once Formed, the NMJ Leaves an Imprint in the Extracellular Matrix Researchers at Work: Neuromuscular Junctions Leave a Residue in the Basal Lamina 6.10. Ion Channels Change Subunits, and Therefore Characteristics, during Development 6.11. Embryonic Synapses Are Sluggish and Slow, Then Become Progressively Faster with Development 6.12. Myelination Extends into Adulthood to Hasten Neuronal Communication 6.13. Myelinating Glia May Prevent Regeneration in the Central Nervous System Summary

CHAPTER 7. Accepting Mortality: Apoptosis 7.1. The Death of Many Cells Is a Normal Process in Development 7.2. The Extent of Death among Developing Motor Neurons Is Regulated by the Size of the Target Researchers at Work: Adding to the Periphery Prevents Apoptosis of Motor Neurons 7.3. Nerve Growth Factor (NGF) Is Discovered to Regulate Apoptosis in Sensory Neurons Researchers at Work: Screening for Nerve Growth Factor Box 7.1. The Controversy over the Nobel Prize for NGF 7.4. NGF Has Both Tropic and Trophic Effects on Selective Neuronal Populations 7.5. The Search for Relatives of NGF Reveals a Family of Neurotrophic Factors and Their Receptors 7.6. Studies in C. Elegans Provide Crucial Information about the Process of Apoptosis Box 7.2. Kerfuffles in Language: Programmed Cell Death Researchers at Work: It Was Suicide, Not Murder 7.7. Apoptosis Involves Active Self- Destruction through a Cascade of "Death Genes" 7.8. Do Motor Neurons Die in ALS for Lack of Neurotrophic Factor(s)? 7.9. Hormones Direct Sexual Differentiation of the Vertebrate Body and Behavior Researchers at Work: Early Exposure to Androgens Organizes the Male Brain 7.10. The Brain Is Also Sexually Dimorphic 7.11. Hormones Can Regulate Apoptosis to Masculinize the Vertebrate Brain Researchers at Work: Sometimes the Tail Wags the Dog 7.12. Sexual Differentiation in Flies Is a Cell-Autonomous Process Researchers at Work: Fruitless Mutants Pursue Unrequited Love 7.13. The Controversy over Sexual Orientation in Flies, Rats, and People Summary

INTERLUDE: The Empiricists Strike Back The Tabula Rasa and the Importance of Experience through the Senses What Does All This Philosophy Stuff Have To Do with This Book?

CHAPTER 8. Synaptic Plasticity: Activity-Guided Neural Development 8.1. Motor Neuronal Death Is Gated by Neuronal Activity 8.2. Developing Muscle Fibers Start Off with Polyneuronal Innervation 8.3. Autonomic Neurons Refine Their Inputs and Outputs 8.4. Donald Hebb Speculated about Neural Plasticity 8.5. Long-Term Potentiation (LTP) Confirms the Existence of Hebbian Synapses Researchers at Work: Cells That Fire Together Wire Together 8.6. A Class of Glutamate Receptors Enforces Hebbian Rules Box 8.1. Does Hippocampal LTP Mediate Learning? 8.7. The Brain Must Integrate Input from the Two Eyes 8.8. Even Spontaneous, Apparently Random Activity Can Provide Order Researchers at Work: Spontaneous Waves of Retinal Activity Form Ocular Dominance Bands in the LGN 8.9. The Gray Matter of Human Cortex Thins as We Mature Summary

CHAPTER 9. Fine-Tuning Sensory Systems: Experience-Guided Neural Development 9.1. Humans Can Adapt to Seeing the World in a New Way 9.2. Retinal Ganglion Cells in Adult Amphibians and Fish Can Reestablish Connections to the Tectum 9.3. Various Permutations of Retinotectal Regeneration Refute a Strict Version of Chemoaffinity 9.4. Visual Experience Fine-Tunes Frog Retinotectal Connections Researchers at Work: Three-Eyed Frogs Show Us the Way 9.5. Mammals Require Visual Experience during a Sensitive Period to Develop Functional Vision 9.6. Physiological Recordings Reveal How Visual Deprivation Impairs Sight Researchers at Work: Strabismus in Kittens Drastically Alters Visual System Connections 9.7. Owls Can Use Visual Experience to Fine-Tune Their Auditory Maps 9.8. Olfactory Receptor Maps Are Also Sculpted by Experience 9.9. Tactile Experience Guides the Formation of Topographic Maps in Somatosensory Cortex Summary

CHAPTER 10. Maximizing Fitness: Socially Guided Neural Development 10.1. The Terms Instinct and Innate Are So Vague That They Are Worthless 10.2. Species with Parental Behavior Develop the Most Complex Brains and Behavior 10.3. Maternal Behavior Can Regulate the Stress Response of Offspring Box 10.1. Kerfuffles in Language: Epigenetic 10.4. Many Species Look to Their Parents to Recognize Mating Partners 10.5. Observational Learning Can Transmit Behaviors across Generations 10.6. Birdsong Is a Learned Behavior Where Young Males Model Their Father's Song Researchers at Work: Sparrows Are Predisposed to Learn Species-Specific Song Elements 10.7. Humans Are Predisposed to Learn Language without Any Formal Training Researchers at Work: The Habituation Response Allows Us to Read Babies' Minds 10.8. Primates Require Love to Develop Properly 10.9. Postnatal Social Stimulation Continues to Affect Brain Development Researchers at Work: Social Stimulation Alters Neuregulin Signaling to Promote Myelination 10.10. Intelligence Tests Demonstrate the Pervasive Effects of Culture 10.11. The Controversial Issue of Racial Differences in Average IQ Performance Researchers at Work: Does Race Affect the IQ of German Offspring of American GIs? Summary

EPILOGUE: Immanuel Kant and the Critique of Pure Reason The a Priori Embodiment of Space and Time What Does All This Philosophy Stuff Have To Do with This Book?

Appendix Glossary References Author Index Subject Index