Foundations of Neural Development offers a unique perspective designed to make complex topics accessible and memorable for undergraduate students. It explores how a single microscopic cell, a human zygote, can develop into the brain--the most complex machine on Earth!

The text is purposefully structured to present topics in the chronological order of brain development. It integrates evolutionary content with philosophical ideas to help students grasp the big picture and aid in learning and retention. Featuring exceptional illustrations and clear explanations, Foundations of Neural Development combines engaging storytelling with rigorous science, guiding students through the intricacies of the topic.

S. Marc Breedlove, the Barnett Rosenberg Professor of Neuroscience at Michigan State University, has written more than 130 scientific articles investigating the role of hormones in shaping the developing and adult nervous system, publishing in journals including Science, Nature, Nature Neuroscience, and the Proceedings of the National Academy of Science. He is also passionate about teaching--in the classroom, and in the greater community through interviews with the Washington Post, Los Angeles Times, New York Times, and Newsweek, as well as broadcast programs including All Things Considered, Good Morning America, and Sixty Minutes. He has active grant support from the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health. Dr. Breedlove is a Fellow of the American Association for the Advancement of Science and the Association for Psychological Science.

Contents

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
I. Preformationism Offered an Easy but Wrong Solution, While Epigenesis Seemed Incomprehensible
II. The Rediscovery of Genes Set the Stage for Understanding Development
III. Gene Expression Directs Cell Differentiation
Researchers at Work: Do Differentiating Cells Dispose of Unused Genes?
1.2. Scientists Domesticated a Simple Worm to Address the Questions of Cell Differentiation
I. Mitotic Lineage Guides Cell Differentiation in Worms
BOX 1.1 Kerfuffles in Language: “Cell fate” and “commitment”
II. Many Embryos, Including All Vertebrates, Display “Self-Regulation”
III. Experimental Embryology Revealed Inductive Processes Underlying Self-Regulation
1.3 A Region of the Vertebrate Embryo Seems to “Organize” Development
Researchers at Work: The Dorsal Lip of the Blastopore Can Organize a New Individual
I. Long Abandoned, the Organizer Was Uncovered through Molecular Biological Techniques
II. What Organizes the Organizer?
III. In Insects, Epidermal Cells Compete to Become Neuroblasts
The Cutting Edge: Tracing the pathway to the human organizer.
Visual Summary

CHAPTER 2 Coordinating Fates: Development of a Body Pattern
2.1 The First Draft of a Body Plan
I. Darwin Noted That Vertebrate Embryos Start Off Looking Alike
Box 2.1. A Step Too Far
RESEARCHERS AT WORK: Two Heads Are Not Better Than One
2.2 Homeotic Mutations and the Homeobox
I. Some Mutations in Drosophila Transform Body Parts Whole
II. Hox Genes Are Crucial for Vertebrate Development, Too
III. Homeobox gene Otx2 specifies the vertebrate forebrain and midbrain
BOX 2.3 Kerfuffles in Language: “Segmentation”
2.3 Defining the Main Axes of the Nervous System
I. Several Signals Designate the Caudal End of the Body and Nervous System
II. 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?
III. Find Out Where You Are to Coordinate your Fate with that of your Neighbors
The Cutting Edge: Brain Organoids
Visual Summary

CHAPTER 3 Upward Mobility: Neurogenesis and Migration
3.1 Generating Neurons
I. The Same Gene May Play a Role in Many Different Developmental Events
II. The Developing Brain Generates Neurons at a Tremendous Rate
III. 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
IIII. The Cerebellum AND Cerebral Cortex Form in Layers
3.2 Cellular Birthdays and Initial Sorting
I. We Can Label Newly Synthesized DNA to Determine the Birthdates of Cells
II. Newborn Cells Shinny Up Glial Poles
RESEARCHERS AT WORK: The Cortex Develops in an Inside-Out Manner
III. A Few Brain Regions Display Continuing Neurogenesis throughout Life
BOX 3.1 THE CONTROVERSY OF NEUROGENESIS IN ADULTHOOD
3.3 Neural Crest and Cerebellum
I. Neural Crest Cells Migrate to Positions throughout the Body
II. Cell Adhesion Molecules Attract and Repel Migrating Cells
III. Cerebellar Granule Cells Parachute Down from Above
RESEARCHERS AT WORK Weaver Neurons Fail to Grasp Glial Fibers
The Cutting Edge: Profiling Gene Expression to Probe Brain Development
Visual Summary

CHAPTER 4 Seeking Identity: Neural Differentiation
4.1 The Differentiation of Neurons and Glia
I. The Fruit Fly Retina Develops through an Orderly Progression of Gene Expression and Signaling
Box 4.1. Transgenics, Knockouts, and Knockins
II. Several Factors Influence Whether a Cell Will Become a Neuron or a Glia
4.2 Differentiation in Spinal Cord and the Periphery
I. The Molecular Differentiation of Motor Neurons Is Orderly
II. Neural Crest Cells Are Affected by Their Migration and Destination
RESEARCHERS AT WORK: Neural Crest Cells Adopt New Fates after Transplantation
RESEARCHERS AT WORK: Targets Can Regulate the Neurotransmitter Phenotype of Afferents
4.3 Evolutionary consequences of increased plasticity
I. 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
II. Later Events in Development Are More Evolutionarily Labile
The Cutting Edge: Artificial Selection for Larger Forebrains
Visual Summary

CHAPTER 5 Feeling One's Way: Axonal Pathfinding
5.1 Axonal Growth Cones Crawl Toward their Targets
I. Ramón y Cajal Described Growth Cones and Discerned Their Significance
II. In Vitro Approaches Reveal Principles of Axonal Growth and Adhesion
RESEARCHERS AT WORK: Getting a Grip: The Role of Adhesion in Axonal Growth
III. Guidance Cues May Be Attractive to One Type of Growth Cone and Repulsive to Others
5.2 Surrounding Cells Provide Guidance Cues
I. Families of Receptors Offer a Multitude of Guidance Cues
II. Pioneer Neurons and Guidepost Cells Establish Pathways for Later Axons
III. Many Axonal Growth Cones Have to Deal with Crossing the Midline
RESEARCHERS AT WORK: What Makes the Floor Plate so Attractive?
5.3 Major Projection Pathways “Read” the Environment
I. Motor Neuronal Axons Must Find the Correct Target Muscles
RESEARCHERS AT WORK: Can You Navigate Your Way Home?
II. The Axons of Retinal Ganglion Cells Must Reach the Midbrain
RESEARCHERS AT WORK: I'd Rather Walk over Here
III. The Corpus Callosum Is Directed across the Midline by a Glial Bridge
RESEARCHERS AT WORK: Glia Can Help Axons Cross a Border
The Cutting Edge: Identifying Callosal Axonal Growth Cones
Visual Summary

CHAPTER 6 Making Connections: Synapse Formation and Maturation
6.1 Signals for Synapse Formation
I. We Can Divide Synapse Structure and Development into Three Parts
II. A Synapse Begins with Adhesion
Researchers at Work: Dendritic Spines Compete for Survival
III. Fragile X Syndrome Suggests There Can Be Too Much of a Good Thing
6.2 Neuromuscular Junction Formation
Researchers at Work: Presynaptic and Postsynaptic Receptors Trigger Synaptic Development
I. Neuromuscular Junctions Illustrate That Synapse Formation Is a Dance for Two (or More)
II. Motor Neuronal Agrin Promotes the Aggregation of Acetylcholine Receptors
III. Neuregulins Boost Local ACHR Expression in Muscle and Maintain Terminal Schwann Cells
IIII. Once Formed, the NMJ Leaves an Imprint in the Extracellular Matrix
Researchers at Work: Neuromuscular Junctions Leave a Residue in the Basal Lamina
6.3 Sharpening Synapses and Myelinating Axons
I. Embryonic Synapses Are Sluggish and Slow, Then Become Progressively Faster with Development
II. Myelination Extends into Adulthood to Hasten Neuronal Communication
III. Myelinating Glia May Prevent Regeneration in the Central Nervous System
The Cutting Edge: A Gene that Increases Alzheimers' Risk Disrupts Myelination
Visual Summary

CHAPTER 7 Accepting Mortality: Apoptosis
7.1. The Death of Many Cells Is a Normal Process in Development
I. 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
II. Motor Neuronal Death Is Gated by Neuronal Activity
7.2 The Hunt for Neurotrophic Factors
I. The Number of Sensory Neurons during Development Mirror that of Motor Neurons
RESEARCHERS AT WORK: Screening for Nerve Growth Factor
II. NGF Has Both Tropic and Trophic Effects on Selective Neuronal Populations
III. The Search for Relatives of NGF Reveals a Family of Neurotrophic Factors and Their Receptors
7.3 The Genetic Pathways of Apoptosis
I. 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
II. Apoptosis Involves Active Self-Destruction through a Cascade of “Death Genes”
III. Do Motor Neurons Die in ALS for Lack of Neurotrophic Factor(s)?
The Cutting Edge: Trophic factors as potential therapy for ALS
Visual 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 Distant Voices: Hormonally-Guided Neural Development
8.1 Hormones Coordinate body-wide changes
I. Hormones Influence Cells by Binding to Receptor Proteins
II. Hormone Release is Regulated by the Brain
III. Insect Stages of Growth are Guided by Two Hormones
IV. Amphibian Metamorphosis is Controlled by Thyroid Hormones
V. Thyroid Hormones are Crucial for Brain Development in Vertebrates
8.2 Sexual Differentiation of the Body and Brain
I. Sexual Differentiation in Flies Is a Cell-Autonomous Process
II. Hormones Direct Sexual Differentiation of the Vertebrate Body and Behavior
RESEARCHERS AT WORK: Early Exposure to Androgens Organizes the Male Brain
III. The Brain Is Also Sexually Dimorphic
IV. Hormones Can Regulate Apoptosis to Masculinize the Vertebrate Brain
RESEARCHERS AT WORK: Sometimes the Tail Wags the Dog
8.3 Comparing the Development of Sexual Behavior in Flies and Humans
RESEARCHERS AT WORK: Fruitless Mutants Pursue Unrequited Love
I. The Controversy over Sexual Orientation in Flies, Rats, and People
The Cutting Edge: Mapping Sex Differences in Gene Expression in the Brain
Summary

CHAPTER 9. Expanding Your Worldview: Activity and Experience-Guided Neural Development
9.1 Activity-Driven Synaptic Elimination and Plasticity
I. Donald Hebb Speculated about Neural Plasticity
II. Long-Term Potentiation (LTP) CONFIRMS the Existence of Hebbian Synapses
Researchers at Work: Cells That Fire Together Wire Together
III. A Class of Glutamate Receptors Enforces Hebbian Rules
BOX 9.1 Dees hippocampal LTP mediate learning?
IV. The Brain Must Integrate Input from the Two Eyes
V. Even Spontaneous, Apparently Random Activity Can Provide Order
Researchers at Work: Spontaneous Waves of Retinal Activity Form Ocular Dominance Bands in the LGN
9.2 Sensory Experience Guides Synaptic Rearrangement
I. Humans Can Adapt to Seeing the World in a New Way
II. Retinal Ganglion Cells in Adult Amphibians and Fish Can Reestablish Connections to the Tectum
III. Various Permutations of Retinotectal Regeneration Refute a Strict Version of Chemoaffinity
IV. Visual Experience Fine-Tunes Frog Retinotectal Connections
Researchers at Work: Three-Eyed Frogs Show Us the Way
V. Mammals Require Visual Experience during a Sensitive Period to Develop Functional Vision
VI. Physiological Recordings Reveal How Visual Deprivation Impairs Sight
Researchers at Work: Strabismus in Kittens Drastically Alters Visual System Connections
9.3 Experience Guides all Developing Sensory Systems
I. Olfactory Receptor Maps Are Also Sculpted by Experience
II. Tactile Experience Guides the Formation of Topographic Maps in Somatosensory Cortex
III. The Gray Matter of Human Cortex Thins as We Mature
THE CUTTING EDGE: Neuronal Activity Guides Cortical Myelination
Visual Summary

CHAPTER 10: Investing in the Next Generation: Socially Guided Neural Development
10.1 Parental Care Evolved to Prolong Brain Development
I. The Terms Instinct and Innate Are So Vague That They Are Worthless
II. Species with Parental Behavior Develop the Most Complex Brains and Behavior
III. Maternal Behavior Can Regulate Gene Expression in their Young
BOX 10.1: Kerfuffles in Language: Epigenetic
10.2 Social Learning Increases Fitness and Reproductive Success
I. Many Species Look to Their Parents to Recognize Mating Partners
II. Observational Learning Can Transmit Behaviors across Generations
III. 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
10.3 Social Stimulation from Peers Supplements Parental Care
I. Humans Are Predisposed to Learn Language without Any Formal Training
Researchers at Work: The Habituation Response Allows Us to Read Babies' Minds
II. Primates Require Love to Develop Properly
III. Postnatal Social Stimulation Continues to Affect Brain Development
Researchers at Work: Social Stimulation Alters Neuregulin Signaling to Promote Myelination
10.4 Social Influences Shape Measures of Human Intelligence
I. Intelligence Tests Demonstrate the Pervasive Effects of Culture
II. The Controversial Issue of Racial Differences in Average IQ Performance
Researchers at Work: Does Race Affect the IQ of German Offspring of American GIs?
III. Is the Heritability of IQ “MIssing” or “Phantom”?
THE CUTTING EDGE: Choosing Designer Babies?
Visual 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
Index

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