• Three Stages of CNS Development
• Neurulation: The Prelude
• The Late Neurula
• Brain & Spinal Cord Development
• Sequential Development of the Regions of the Human Brain
• The End Product: The Human Brain
• Two Main Cell Types: Neurons & Glia
• Stratification & Cell Differentiation
• The Outgrowth of the Nerve Axon Towards Its Target Tissue
• Experiments Showing The Role of the Cytoskeleton in Axonal Outgrowth
• Neurotrophic Factors
• Experiments to Show NGF Promotes Neuron Outgrowth & Survival
• Nerve Pathways are Precisely Defined
• Final Comments

• Neurogenesis
• Axon & Dendrite Outgrowth
• Synapse Refinement (Not covered)

• Chordamesoderm "induces" neural plate
• Neural plate folds to form neural tube
• Neural tube will form brain (anterior end) & spinal cord (posterior)
• How do you convert a hollow one-cell layer thick tube into a complex multilayered brain & spinal cord?

• Neural Tube: One layer of cells surrounding a lumen & covered by external limiting membrane
• Neural Crest have separated out--begun to migrate
• Neural Tube thickens & folds to form brain
• New layers of nerve cells will appear in brain & spinal cord (neurogenesis)

• Cranial & caudal neuropores are last to close
• Even prior to this 3 Brain regions evident at 3 1/2 wks:
• Prosencephalon (forebrain),
• Mesencephalon (midbrain),
• Rhombencephalon (hindbrain)
• Spinal cord does not fold

Here's a graphic representation of the derivation of each brain region during human development.

Clearly a lot of changes are required to convert the anterior portion of the neural tube into the fully formed human brain.

• 1 x 1011 neurons in CNS
• More neurons in embryo than adult!
• Glia serve supportive function
• More recently glia serve other critical roles
• Glia outnumber neurons; 1 x 1012 in CNS
• Outgrowths for both occur at "Growth Cones"

• Neuroepithelium of neural tube is one cell layer thick
• Cells of neural tube are Stem Cells
• Neuroepithelial stem cells divide to form Neuroblasts (specialized stem cells committed to neuron formation) and glioblasts (specialized stem cells committed to glial cell formation)
• Neuroblasts & glioblasts move radially away from lumen leading to stratification of CNS that is characteristic for each region

• Neurons grow by extending "Growth Cones"
• "Growth Cone" looks just like the leading edge of moving white blood cell
• Rich in actin filaments
• Extends "ruffling membrane" & filopodia
• Movement directed by cellular contacts & ECM
• Growth is promoted by "Neurotrophic Factors"

• Microtubules are essential for neuronal outgrowth
• Microfilaments are essential for neuronal outgrowth

• Secreted proteins that stimulate neuron outgrowth & survival
• Nerve Growth Factor (NGF) was first known & is most studied
• Rita Levi-Montalcini was awarded Nobel Prize for her pioneering work on NGF

Effects of NGF on Cell Outgrowths: Tissue Culture of Sympathetic Ganglia

• Figure Shows nerve pathways in left & right chick limbs
• Near perfect mirror-image symmetry
• Thus, neurons follow precisely defined paths

• The transformation of the neural tube into the brain & spinal cord is a complex process
• It involves cell division (more cells), differentiation and morphogenesis
• Stem cells form precursors of neuronal and glial cell types
• NGF oversees survival and outgrowth of neuron
• Precise pathways delineate where nerve cells will grow