The Developing Brain and its Connections

Cover
Half Title
Title
Copyright
Dedication
Brief Contents
Detailed Contents
List of Boxes
Author Biography
Preface
Chapter 1 An Introduction to the Field of Developmental Neurobiology
Cellular Structures and Anatomical Regions of the Nervous System
The Central and Peripheral Nervous Systems Are Comprised of Neurons and Glia
The Nervous System Is Organized around Three Axes
Origins of CNS and PNS Regions
The Vertebrate Neural Plate Gives Rise to Central and Peripheral Structures
Future Vertebrate CNS Regions Are Identified at Early Stages of Neural Development
The Timing of Developmental Events Is Standardized in Many Vertebrates
Anatomical Regions and the Timing of Developmental Events Are Mapped in Invertebrate Nervous Systems
The Drosophila CNS and PNS Arise from Distinct Areas of Ectoderm
Cell Lineages Can Be Mapped in C. Elegans
Gene Regulation in the Developing Nervous System
Experimental Techniques Are Used to Label Genes and Proteins in the Developing Nervous System
Altering Development Helps Understand Normal Processes
Using Naturally Occurring Events to Understand Neural Development
Summary
Further Reading
Chapter 2 Neural Induction
Neural Tissue is Designated During Embryogenesis
Gastrulation Creates New Cell and Tissue Interactions That Influence Neural Induction
Neural Induction: Early Discoveries
Amphibian Models Were Used in Early Neuroembryology Research and Remain Popular Today
A Region of the Dorsal Blastopore Lip Organizes the Amphibian Body Axis and Induces the Formation of Neural Tissue
The Search for the Neural Inducer Took Decades of Research
New Tissue Culture Methods and Cell-Specific Markers Advanced the Search for Neural Inducers
Neural Induction: The Next Phase of Discoveries
Studies Suggest Neural Induction Might Require Removal of Animal Cap-Derived Signals
Mutation of the Activin Receptor Prevents the Formation of Ectoderm and Mesoderm but Induces Neural Tissue
Modern Molecular Methods Led to the Identification of Three Neural Inducers
Noggin, Follistatin, and Chordin Prevent Epidermal Induction
Studies of Epidermal Induction Revealed the Mechanism for Neural Induction
The Discovery of Neural Inducers in the Fruit Fly Drosophila Led to a New Model for Epidermal and Neural Induction
BMP Signaling Pathways Are Regulated by SMADs
Additional Signaling Pathways May Influence Neural Induction in Some Contexts
Additional Neural Induction Pathways May Be Used in Some Species
Summary
Further Reading
Chapter 3 Segmentation of the Anterior–Posterior Axis
Neural Tube Formation
Early Segmentation of the Neural Tube Establishes Subsequent Organization
Temporal–Spatial Differences in Organizer-Derived Signals Induce Head and Tail Structures
Activating, Transforming, and Inhibitory Signals Interact to Pattern the A/P Axis
Specification of Forebrain Regions
Signals from Extraembryonic Tissues Pattern Forebrain Areas
Forebrain Segments Are Characterized by Different Patterns of Gene Expression
Signals Prevent Wnt Activity in Forebrain Regions
Regionalization of the Mesencephalon and Metencephalon Regions
Intrinsic Signals Pattern the Midbrain–Anterior Hindbrain
Multiple Signals Interact to Pattern Structures Anterior and Posterior to the Isthmus
FGF Is Required for Development of the Cerebellum
FGF Isoforms and Intracellular Signaling Pathways Influence Cerebellar and Midbrain Development
FGF and Wnt Interact to Pattern the A/P Axis
Rhombomeres: Segments of the Hindbrain
Cells Usually Do Not Migrate between Adjacent Rhombomeres
Multiple Signals Interact to Regulate Krox20 and EphA4 Expression in r3 and r5
Hox Genes Regulate Hindbrain Segmentation
The Body Plan of Drosophila Is a Valuable Model for Studying Segmentation Genes
The Homeotic Genes That Establish Segment Identity Are Conserved across Species
Transcription Factors Regulate Hox Gene Expression and Rhombomere Identity
Retinoic Acid Regulates Hox Gene Expression
The RA-Degrading Enzyme Cyp26 Helps Regulate Hox Gene Activity in the Hindbrain
RA and FGF Differentially Pattern Posterior Rhombomeres and Spinal Cord
Cdx Transcription Factors Are Needed to Regulate Hox Gene Expression in the Spinal Cord
The Activation-Transformation Model Is Being Revised
Summary
Further Reading
Chapter 4 Patterning along the Dorsal–Ventral Axis
Anatomical Landmarks and Signaling Centers in the Posterior Vertebrate Neural Tube
The Sulcus Limitans Is an Anatomical Landmark That Separates Sensory and Motor Regions
Labeling Techniques Identify Cell Types along the D/V Axis
The Roof Plate and Floor Plate Produce Signals That Influence D/V Patterning
Roof Plate and Floor Plate Signals Influence Gene Expression Patterns along the D/V Axis of the Neural Tube
Ventral Signals and Motor Neuron Patterning in the Posterior Neural Tube
The Notochord Is Required to Specify Ventral Structures
Sonic Hedgehog (Shh) Is Necessary for Floor Plate and Motor Neuron Induction
Shh Concentration Differences Regulate Induction of Ventral Neuron Subtypes
Genes Are Activated or Repressed by the Shh Gradient
Shh Binds to and Regulates Patched Receptor Expression
Shh Signals Interact to Influence Gene Expression and Ventral Patterning
RA and FGF Signals Are Also Used in Ventral Patterning
Dorsal Patterning in the Posterior Neural Tube
TGFβ-Related Molecules Help Pattern the Dorsal Neural Tube
Roof Plate Signals Pattern a Subset of Dorsal Interneurons
BMP-Related Signals Pattern Class A Interneurons
BMP-Signaling May Influence Dorsal Cell Specification in Multiple Ways
BMP-Like Signaling Pathways Are Regulated by SMADS
Wnt Signaling through the β-Catenin Pathway Influences Development in the Dorsal Neural Tube
BMP and Shh Antagonize Each Other to Form D/V Regions of the Neural Tube
D/V Patterning in the Anterior Neural Tube
Roof Plate Signals Interact with the Shh Signaling Pathway in the Cerebellum, Diencephalon, and Telencephalon
Zic Mediates D/V Axis Specification by Integrating Dorsal and Ventral Signaling Pathways
The Location of Cells along the A/P Axis Influences Their Response to Ventral Shh Signals
Analysis of Birth Defects Reveals Roles of D/V Patterning Molecules in Normal Development
Summary
Further Reading
Chapter 5 Proliferation and Migration of Neurons
Neurogenesis and Gliogenesis
Scientists Debated Whether Neurons and Glia Arise from Two Separate Cell Populations
Neuroepithelial Cell Nuclei Travel between the Apical and Basal Surfaces
Interkinetic Movements Are Linked to Stages of the Cell Cycle
Cell Proliferation and Migration Are Influenced by the Cell Division Plane
Distinct Proteins Are Concentrated at the Apical and Basal Poles of Progenitor Cells
The Rate of Proliferation and the Length of the Cell Cycle Change over Time
Cellular Migration in the Central Nervous System
In the Neocortex, Newly Generated Neurons Form Transient Layers
Most Neurons Travel along Radial Glial Cells to Reach the Cortical Plate
Cells in the Cortical Plate Are Layered in an Inside-Out Pattern
The Reeler Mutation Displays an Inverted Cell Migration Pattern
Cajal–Retzius Cells Release the Protein Reelin, a Stop Signal for Migrating Neurons
Cortical Interneurons Reach Target Areas by Tangential Migration
Cell Migration Patterns in the Cerebellum Reflect Its Distinctive Organization
Cerebellar Neurons Arise from Two Zones of Proliferation
Granule Cell Migration from External to Internal Layers of the Cerebellar Cortex Is Facilitated by Astrotactin and Neuregulin
Mutant Mice Provide Clues to the Process of Neuronal Migration in the Cerebellum
Migration in the Peripheral Nervous System: Examples From Neural Crest Cells
Neural Crest Cells Emerge from the Neural Plate Border
Neural Crest Cells from Different Axial Levels Contribute to Specific Cell Populations
Cranial Neural Crest Forms Structures in the Head
Multiple Mechanisms Are Used to Direct Neural Crest Migration
Trunk Neural Crest Cells Are Directed by Permissive and Inhibitory Cues
Melanocytes Take a Different Migratory Route Than Other Neural Crest Cells
Summary
Further Reading
Chapter 6 Cell Determination and Early Differentiation
Lateral Inhibition and Notch Receptor Signaling
Lateral Inhibition Designates Future Neurons in Drosophila Neurogenic Regions
Lateral Inhibition Designates Stripes of Neural Precursors in the Vertebrate Spinal Cord
Cellular Determination in the Invertebrate Nervous System
Cells of the Drosophila PNS Arise from Epidermis and Develop in Response to Differing Levels of Notch Signaling Activity
Ganglion Mother Cells Give Rise to Drosophila CNS Neurons
Apical and Basal Polarity Proteins Are Differentially Segregated in GMCs
Cell Location and Temporal Transcription Factors Influence Cellular Determination
Mechanisms Underlying Fate Determination in Vertebrate CNS Neurons
Coordinating Signals Mediate the Progressive Development of Cerebellar Granule Cells
Temporally Regulated Transcription Factor Networks Help Mediate the Fate of Cerebral Cortical Neurons
Epigenetic Factors Influence Determination and Differentiation in Vertebrate Neurons
Determination and Differentiation of Neural Crest-Derived Neurons
Environmental Cues Influence the Fate of Parasympathetic and Sympathetic Neurons
Sympathetic Neurons Can Change Neurotransmitter Production Later in Development
Determination of Myelinating Glia in the Peripheral and Central Nervous System
Neuregulin Influences Determination of Myelinating Schwann Cells in the PNS
Precursor Cells in the Optic Nerve Are Used to Study Oligodendrocyte Development
Internal Clocks Establish When Oligodendrocytes Will Start to Form
Development of Specialized Sensory Cells
Cell–Cell Contact Regulates Cell Fate in the Compound Eye of Drosophila
Cell–Cell Contacts and Gene Expression Patterns Establish R1–R7 Photoreceptor Cell Types
Cells of the Vertebrate Inner Ear Arise from the Otic Vesicle
Notch Signaling Specifies Hair Cells in the Organ of Corti
Cells of the Vertebrate Retina Are Derived from the Optic Cup
The Vertebrate Retina Cells Are Generated in a Specific Order and Organized in a Precise Pattern
Temporal Identity Factors Play a Role in Vertebrate Retinal Development
Summary
Further Reading
Chapter 7 Neurite Outgrowth, Axonal Pathfinding, and Initial Target Selection
Growth Cone Motility and Pathfinding
Early Neurobiologists Identify the Growth Cone as the Motile End of a Nerve Fiber
In Vitro and In Vivo Experiments Confirm Neurite Outgrowth from Neuronal Cell Bodies
Substrate Binding Influences Cytoskeletal Structures to Promote Growth Cone Motility
Actin-Binding Proteins Regulate Actin Polymerization and Depolymerization
Rho Family GTPases Influence Cytoskeletal Dynamics
Growth Cone Substrate Preferences in Vitro and in Vivo
In Vitro Studies Confirm That Growth Cones Actively Select a Favorable Substrate for Extension
Extracellular Matrix Molecules and Growth Cone Receptors Interact to Direct Neurite Extension
Pioneer Axons and Axonal Fasciculation Aid Pathway Selection
Research in Invertebrate Models Leads to the Labeled Pathway Hypothesis
Fasciclins Are Expressed on Axonal Surfaces
Vertebrate Motor Neurons Rely on Local Guidance Cues
Several Molecules Help Direct Motor Axons to Muscles
Intermediate, Midline Targets for Spinal Commissural Axons
The Axons of Vertebrate Commissural Interneurons Are Attracted to the Floor Plate
Laminin-Like Midline Guidance Cues Are Found in Invertebrate and Vertebrate Animal Models
Homologous Receptors Mediate Midline Attractive and Repulsive Guidance Cues
Slit Proteins Provide Additional Axonal Guidance Cues at the Midline
Slit Proteins Repel Commissural Axons away from the Midline by Activating Robo Receptors
Robo Signaling Is Regulated by Additional Proteins Expressed on Commissural Axons
Shh Phosphorylates Zip Code Binding Proteins to Increase Local Translation of Actin and Direct Growth of Vertebrate Commissural Axons
The Retinotectal System and the Chemoaffinity Hypothesis
Early Studies of Axon-Target Recognition Focused on Physical Cues and Neural Activity
Amphibian Retinal Ganglion Cell Axons Regenerate to Reestablish Neural Connections
Retinotectal Maps Are Found in Normal and Experimental Conditions
Some Experimental Evidence Contradicts the Chemoaffinity Hypothesis
A “Stripe Assay” Reveals Growth Preferences for Temporal Retinal Axons
Retinotectal Chemoaffinity Cues Are Finally Identified in the 1990s
Eph/Ephrin Signaling Proves to Be More Complex Than Originally Thought
Axonal Self-Avoidance as a Mechanism for Chemoaffinity
Summary
Further Reading
Chapter 8 Neuronal Survival and Programmed Cell Death
Growth Factors Regulate Neuronal Survival
The Death of Nerve Cells Was Not Initially Recognized as a Normal Developmental Event
Studies Reveal That Target Tissue Size Affects the Number of Neurons That Survive
Some Tumor Tissues Mimic the Effect of Extra Limb Buds on Nerve Fiber Growth
In Vitro Studies Led to a Bioassay Method to Study Nerve Growth Factors
The Factor Released by Sarcoma 180 Is Found to Be a Protein
Nerve Growth Factor Is Identified in Salivary Glands
Studies of NGF Lead to the Discovery of Brain-Derived Neurotrophic Factor
Discoveries of Other NGF-Related Growth Factors Rapidly Followed
NGF Signaling Mechanisms and Neurotrophin Receptors
NGF Is Transported from the Nerve Terminal to the Cell Body
NGF Receptors Are First Identified in the PC12 Cell Line
Activation of Trk Receptors Stimulates Multiple Intracellular Signaling Pathways
Full-Length Trk Receptors Interact with Truncated Trk Receptors and p75NTR to Influence Cell Survival
Other Growth Factors Also Regulate Neuronal Survival and Outgrowth
Ciliary Neurotrophic Factor Is Isolated Based on an Assay for Developing Ciliary Ganglion Neurons
The CNTF Receptor Requires Multiple Components to Function
Growth Factors Unrelated to CNTF Promote Survival of Developing CG and Motor Neurons
Programmed Cell Death During Neural Development
Studies Reveal Cell Death Is an Active Process Dependent on Protein Synthesis
Cell Death Genes Are Identified in C. Elegans
Homologs of the C. Elegans Ced and Egl Genes Contribute to the Mammalian Apoptotic Pathway
p75NTR and Precursor Forms of Neurotrophins Help Mediate Neuronal Death during Development
Summary
Further Reading
Chapter 9 Synaptic Formation and Reorganization Part I: The Neuromuscular Junction
Chemical Synapse Development in the Peripheral and Central Nervous Systems
Reciprocal Signaling Leads to the Development of Unique Synaptic Elements in Presynaptic and Postsynaptic Cells
The Vertebrate Neuromuscular Junction as a Model for Synapse Formation
At the NMJ, the Presynaptic Motor Axon Releases Acetylcholine to Depolarize the Postsynaptic Muscle Cell
The Distribution of AChRs Is Mapped in Developing Muscle Fibers
The Density of Innervation to Muscle Fibers Changes during Vertebrate Development
The Synaptic Basal Lamina Is a Site of NMJ Organizing Signals
AChRs Cluster Opposite Presynaptic Nerve Terminals in Response to Agrin Released by Motor Neurons
The Agrin Hypothesis Is Revised Based on Additional Observations
The Receptor Components MuSK and LRP4 Mediate Agrin Signaling
Rapsyn Links AChRs to the Cytoskeleton
AChR Subunits Are Synthesized in Nuclei Adjacent to the Nerve Terminal
Perisynaptic Schwann Cells Play Roles in NMJ Synapse Formation and Maintenance
The Synaptic Basal Lamina Concentrates Laminins Needed for Presynaptic Development and Alignment with Postjunctional Folds
Models of Synaptic Elimination in the NMJ
The Relative Levels of Neuromuscular Activity Determine Which Terminal Branches Remain at the Endplate
BDNF and Pro-BDNF Are Candidates for the Protective and Punishment Signals
Perisynaptic Schwann Cells Influence the Stability of Synaptic Connections
Summary
Further Reading
Chapter 10 Synaptic Formation and Reorganization Part II: Synapses in the Central Nervous System
Excitatory and Inhibitory Synapses in the Central Nervous System
Many Presynaptic and Postsynaptic Elements Are Similar in Excitatory and Inhibitory Synapses
The Postsynaptic Density Is an Organelle Found in Excitatory, but Not Inhibitory, Synapses
Cell Adhesion Molecules Mediate the Initial Stabilization of Synaptic Contacts
Neurexins and Neuroligins Also Induce Formation of Synaptic Elements and Stabilize Synaptic Contacts
Reciprocal Signals Regulate Pre- and Postsynaptic Development
Dendritic Spines Are Highly Motile and Actively Seek Presynaptic Partners
BDNF Influences Dendritic Spine Motility and Synaptogenesis
Eph/Ephrin Bidirectional Signaling Mediates Presynaptic Development
Eph/Ephrin Signaling Initiates Multiple Intracellular Pathways to Regulate the Formation of Postsynaptic Spine and Shaft Synapses
Wnt Proteins Influence Pre- and Postsynaptic Specializations in the CNS
Different Wnts Regulate Postsynaptic Development at Excitatory and Inhibitory Synapses
Glial Cells Contribute to CNS Synaptogenesis
Synapse Elimination and Reorganization in the CNS
The Vertebrate Visual System Is a Popular Model to Study Synapse Elimination and Reorganization
Spontaneous Waves of Retinal Activity Stabilize Selected Synapses in LGN Layers
Competition between Neurons Determines Which Synaptic Connections Are Stabilized
Early Visual Experience Establishes Ocular Dominance Columns in the Primary Visual Cortex
Homeostatic Plasticity Contributes to Synaptic Activity
Intrinsic and Environmental Cues Continue to Influence Synapse Organization at All Ages
Summary
Further Reading
Glossary
Index