Development of the Nervous System

It presents a broad outline of neural development principles as exemplified by key experiments and observations from past and recent times. The text is organized along a development pathway from the induction of the neural primordium to the emergence of behavior. It covers all the major topics including the patterning and growth of the nervous system, neuronal determination, axonal navigation and targeting, synapse formation and plasticity, and neuronal survival and death.

Table of Contents:
1. Neural induction

Development and evolution of neurons

Early embryology of metazoans

Derivation of neural tissue

Interactions with neighboring tissues in making neural tissue

The molecular nature of the neural inducer

Conservation of neural induction

Interactions among the ectodermal cells in controlling neuroblast segregation

Summary

2. Polarity and segmentation

Regional identity of the nervous system

The anterior-posterior axis and hox genes

Hox gene function in the vertebrate nervous system

Signaling molecules that pattern the anterior-posterior axis in vertebrates: heads or tails

Organizing centers in the developing brain

Forebrain development, prosomeres, and pax genes

Dorsal-ventral polarity in the neural tube

Dorsal neural tube and neural crest

Patterning the cerebral cortex

Summary

3. Genesis and migration

What determines the number of cells produced by the progenitors?

The generation of neurons and glia

Cerebral cortex histogenesis

Cerebellar cortex histogenesis

Molecular mechanisms of neuronal migration

Postembryonic and adult neurogenesis

Summary

4. Determination and differentiation

Transcriptional hierarchies in invariant lineages: C. elegans neurons

Spatial and temporal coordinates of determination: drosophila CNS neuroblasts

Asymmetric cell divisions and asymmetric fate

Generating complexity through cellular interactions: the drosophila retina

Specification and differentiation through cellular interactions and interactions with the local environment: the vertebrate neural crest

Competence and histogenesis: the mammalian cortex

The interplay of intrinsic and extrinsic influences in histogenesis: the vertebrate retina

Interpreting gradients and the spatial organization of cell types: spinal motor neurons

Summary

5. Axon growth and guidance

The growth cone

The dynamic cytoskeleton

Dendrite formation

What do growth cones grow on?

What provides directional information to growth cones?

Cell adhesion and labeled pathways

Repulsive guidance

Chemotaxis, gradients, and local information

Signal transduction

The midline: to cross or not to cross?

Attraction and repulsion: desensitization and adaptation

The optic pathway: getting there from here

Summary

6. Target selection

Defasciculation

Target recognition and target entry

Slowing down and branching in the target region

Border patrol: the prevention of inappropriate targeting

Topographic mapping

Chemospecificity and ephrins

The third dimension, lamina-specific termination

Cellular and synaptic targeting

Sniffing out targets

Shifting and fine tuning of connections

Summary

7. Naturally-occurring neuron death

What does neuron death look like?

Early elimination of progenitor cells

How many differentiated neurons die?

Survival depends on the synaptic target

NGF: a target-derived survival factor

The neurotrophin family

The trk family of neurotrophin receptors

How does the neurotrophin signal reach the soma?

The p75 neurotrophin receptor can initiate cell death

Cytokines act as neuron survival factors

Hormonal control of neuron survival

Cell death requires protein synthesis

Intracellular signaling pathways that mediate survival

Intracellular signaling pathways that mediate death

Caspases: agents of death

Bcl-2 proteins: regulators of programmed cell death

Removal of dying neurons

Synaptic transmission at the target

Afferent regulation of neuron survival

Intracellular calcium mediates both survival and death

Summary

8. Synapse formation and function

What do newly formed synapses look like?

Where Do Synapses Form on the Postsynaptic Cell?

How Rapidly Are Synapses Added to the Nervous System?

The first signs of synapse function

The decision to form a synapse

The sticky synapse

Converting growth cones to presynaptic terminals

Receptor clustering and postsynaptic differentiation at the NMJ

Agrin is a transynaptic clustering signal at the NMJ

Receptor clustering signals in the CNS

Scaffold proteins and receptor aggregation in the CNS

Innervation increases receptor expression and insertion

Synaptic activity regulates receptor density

Maturation of transmission and receptor isoform transitions

Maturation of transmitter reuptake

Short-term plasticity

Appearance of synaptic inhibition

Is inhibition really inhibitory during development?

Summary

9. Refinement of synaptic connections

The early pattern of connections

Functional synapses are eliminated

Many axonal arborizations are eliminated or refined

The Sensory Environment Influences Synaptic Connections

Activity Influences Synapse Elimination at the NMJ

Synapse refinement is reflected in sensory coding properties

Activity contributes to topography and the alignment of maps

Spontaneous activity and afferent refinement

Critical periods: enhanced plasticity during development

Heterosynaptic Depression and Synapse Elimination

Involvement of intracellular calcium

Calcium-activated second messenger systems

Gain control

Homeostatic plasticity: the more things change, the more they stay the same

Plasticity of inhibitory connections

Synaptic influence on neuron morphology

Summary

10. Behavioral development

Behavioral ontogeny

The first movements are spontaneous

The mechanism of spontaneous movements

More complex behavior is assembled from the integration of simple circuits

The role of activity in the emergence of coordinated behavior

Stage-specific behaviors

Genetic determinants of behavior

Environmental determinants of behavioral development

Beginning to make sense of the world

Asking babies questions (and getting some answers!)

Acute hearing

Sharp eyesight

Sex-specific behavior

Genetic sex

Hormonal control of brain gender

Singing in the brain

Genetic control of brain gender in flies

From Genome to Brain Gender in Vertebrates?

Genomic Imprinting: The Ultimate in Parental Control

Hit the Ground Learning

Learning preferences from aversions

Skill Learning: It Don’t Come Easy

Getting information from one brain to another

Language

Summary

Molecules and Genes Index