Neurodevelopment and the Dynamic Brain

Question 1

Neural Stem Cells

Answer 1

Multipotential cell, lining the neural tube, extensive capacity for self-renewal.

In adults, neural stem cells line the ventricles forming the sub ventricular zone.

They give rise to PROGENITOR CELLS.

Question 2

Progenitor Cells

Answer 2

Progenitor cells can also divide, however they eventually produce non-dividing cells:

Neuroblasts and Glioblasts.

Sam Weiss discovered that stem cells remain capable of producing neurons and glia throughout adulthood and even in aging brain.

Therefore, neurons that die in an adult brain should be replaceable.

Prolactin, Gene Transcription, Epigenetics are involved in ensuring stem cells become mature neurons/glia.

Question 3

Neuroblasts (Non-Dividing Progenitor Cells)

Answer 3

Develop into mature neurons.

Question 4

Glioblasts (Non-Dividing Progenitor Cells)

Answer 4

Develop into mature glia.

Question 5

Prolactin (Maturity of Neurons/Glia)

Answer 5

Naturally occurring hormone that helps replace lost neurons in animal models.

Question 6

Gene Transcription (Maturity of Neurons/Glia)

Answer 6

Turning on the correct genes that dictates a stem cell will become a neuron and not a skin cell.

Question 7

Epigenetics (Maturity of Neurons/Glia)

Answer 7

Different cells have different gene expression, leading synthesis of different proteins and ultimately different phenotypes.

DNA methylation: a methyl group is attached to the DNA to turn off gene transcription. It alters gene expression dramatically during development. Different methylation patterns are needed to trigger the differentiation of STEM cells.

Methylation patterns are influenced by neighboring cells, chemicals, stress, etc.

Question 8

Neurotrophic Factors

Answer 8

Chemical compounds that act to support growth and differentiation of neurons.

Keeps adult neurons alive and healthy.

Epidermal Growth Factor stimulates stem cells to produce Progenitor Cells.

Basic Fibroblast Growth Factor stimulates progenitor cells to produce Neuroblasts.

Neuroblasts serve as an all-purpose neuron until they are exposed to certain growth factors in other areas.

These chemical messengers will dictate the ultimate fate of the neuron.

Question 9

What are the neurodevelopmental stages?

Answer 9

Cell Birth, Cell Migration, Cell Differentiation, Cell Maturation, Synaptogenesis, Cell Death, Myelogenesis.

Question 10

Cell Birth (Neurogenesis, Gliogenesis)

Answer 10

Neurogenesis is largely complete by 5 months, and during this time, the brain is resilient to injuries and/or trauma.

Question 11

Cell Migration

Answer 11

Begins just after neurogenesis is complete; lasts for 6 weeks.

Question 12

Cell Differentiation

Answer 12

Begins after migration is complete; more or less complete at time of birth.

Question 13

Cell Maturation (Dendritic Development, Axonal Growth)

Answer 13

This process occurs for years, well into adulthood; growth of dendrites and axons.

Question 14

Synaptogenesis (Formation of Synapses)

Answer 14

Each neuron begins forming its own networks.

Can synapse with hundreds or thousands of other neurons.

Question 15

Cell Death

Answer 15

If you don’t use it, you lose it.

Question 16

Myelogenesis (Formation of Myelin)

Answer 16

Neuronal Networks become more efficient in their communication.

Sign of neurodevelopmental maturity.

Occurs well into adulthood.

Question 17

Subventricular Zone

Answer 17

Contains a primitive map of the Cerebral Cortex.

Cells formed in certain regions of the SVZ migrate to certain cortical locations.

Question 18

Radial Glial Cells

Answer 18

Form a path that extends from the SVZ to the surface of the cortex.

Undifferentiated progenitor cells follow this path.

Question 19

How do cells get to their final destination?

Answer 19

Cortical layers form from inside out.

Most inner layers are first to form.

Intracellular signals progressively restrict the choice of traits a cell can express.

Therefore, the emergence of a cell type is a combination of genetic instructions, timing and signals from neighboring cells in the local environment.

Question 20

What does a maturing neuron need?

Answer 20

Dendrites, Axon, Growth Cones, and Filopod.

Question 21

Dendrites

Answer 21

Provide surface area for synapse formation.

Branching of dendrites.

Growth of dendritic spines.

Question 22

Axon

Answer 22

Extending to appropriate target to initiate synapse formation.

Occurs very rapidly.

Various molecules attract or repel axon tip, thus guiding it through a very complex terrain.

Question 23

Growth Cones

Answer 23

These are growing axons.

They are a response to:
Cell-Adhesion Molecules - Secreted from cell or lie on cell surface.

Tropic Molecules - Secreted from target cells and carry a “come here” or “go away” message. Netrin is the only known group.

Question 24

Filopod

Answer 24

Growth cones extend shoots called filopod.

When filoppod reaches an appropriate target, the others follow.

Question 25

Synaptic Pruning

Answer 25

The brain uses apoptosis as a method of pruning.

Genetic signals, experience, hormones, stress, etc. are all factors that can initiate apoptosis.

~42% of all synapses in human cortex are lost.

Neurons become dependent on their target cell and will die without them.

Nerve Growth Factor is a neurotrophic factor produced by cells that regulate neuronal survival.

Neurons that are deprived of NGF will undergo apoptosis.

Cortex continues to thin from ages 5 to20.

Question 26

What is Neural Darwinism?

Answer 26

Competition drives neuronal loss.

Environmental pressure leads to competition amongst neurons.

Question 27

Myelination

Answer 27

Frontal Lobe is the last brain region to mature (pruning occurs into the 20’s).

This process can be used as an index of neuronal activity.

Early-Myelinating areas control simple movement, while late-myelinating areas control neuronal maturity.