Mechanisms of Neural Development

Question 1

What are the 5 stages of neural development?

Answer 1

1. Neurogenesis
2. Migration + differentiation
3. Axon guidance
4. Synaptogenesis
5. Activity-dependent refinement

Question 2

What is neurogenesis?

Answer 2

Creating the right number of nerve cells

Question 3

The neural tube starts a single layer of replicating neuroepithelial cells. What are the two surfaces of this single layer?

Answer 3

• Plial (outer) surface
• Luminal (ventricular) surface

Question 4

How do neuroepithelial cells replicate to start with?

Answer 4

• Neuroepithelial cell drops down to luminal surface
• Divides perpendicular to luminal surface
• Forms another neuroepithelial cell next to original copy

Question 5

Shortly after the neural tube has sealed, there are enough neuroepithelial cells - what happens next?

Answer 5

• Symmetric divison switches to asymmetric
• Neuroepithelial cell drops down
• Divides parrallel to lumen rather than perpendicular
• Forms a neuroblast rather than another neuroepithelial cell
• Neuroblast = newly developed nerve cell

Question 6

What happens to patients with microcephaly?

Answer 6

They have small brains - due to loss of microcephalin protein, which is needed to produce sufficient nerve cells.

Have severe learning difficulty, but specific neurological deficits are rare.

Question 7

What is migration and differentiation?

Answer 7

Getting the cells to the right place

Question 8

What do morphogens do?

Answer 8

Control what type of cells are produced

Question 9

What directs neuroblast migration?

Answer 9

Chemical guidance signals eg. neuregulins, semaphorins

Question 10

So how is the cerebral cortex developed (neuroblast, layers, direction)?

Answer 10

• The neuroblast migrates straight up to the pial surface
• Marginal zone is formed (remains at pial surface)
• Subplate is formed (moves down)
• Both marginal and subplate act as directors/guidance
• Extra layers are added underneath the marginal plate eg. cortical plate
• This way cortical layers are created from inside to outside
• Resulting laters = superficial, middle, deep

Question 11

What is lissencephaly?

Answer 11

Loss of reelin, reelin is needed as a signal molecule, without it the cortex develops the wrong way (from outside to in) so cortex too thick.

Leads to learning difficulties and epilepsy.

Question 12

In axon guidance, what are the growth tips of neurites called?

Answer 12

Growth cones - carry receptors for chemical signals

Question 13

What molecule is important for supporting filipodia (located in growth cones)?

Answer 13

Actin bundles

Question 14

Describe what happens when the chemical guidance signals bind to the receptors in the growth cones

Answer 14

There are two different receptors:

Attractive guidance - receptor that increases actin filament (growing)

Repulsive guidance - receptor that shrinks actin filament

This helps to grow the axon in a particular direction if both receptors are activated in different places / opposite ends.

Question 15

What happens to people lacking key growth cone receptors?

Answer 15

Develop abnormal, ipsilateral sensory and motor pathways

Question 16

Growth cones can only grow through tissues that they can stick to. How do filopodia bind to the extracellular matrix?

Answer 16

Extracellular matrix has matrix proteins - eg. laminin

There are matching binding molecules on the growing filopodia - eg. integrin, which is a matching binding molecule.

Integrin can then bind to laminin and grow through that particular area.

Question 17

What is heterotopia and what causes it?

Answer 17

Caused by loss/mutation of doublecortin protein -> forms a double cortex, can lead to normal intellect to severe learning difficulties plus epilepsy.

Question 18

Axons explore their target region by making ‘trial’ contacts with cells. What happens when a trial contact succeeds?

Answer 18

1. Filipodia extend from dendrites, seeking contact from passing axons
2. Complementary surface proteins link and stabilise contact (eg. neuroligin-1 and B-neurexin)
3. Triggering formation of synaptic structures

Question 19

Axons explore their target region by making ‘trial’ contacts with cells. What happens when a trial contact fails?

Answer 19

If surface molecules can’t bind to one another, the filopodium retracts

(eg. 1a afferents and antagonist motor neurones)

Question 20

What is activity dependent refinement?

Answer 20

Testing and perfecting the neural circuit

Question 21

New synapses have few working glutamate receptors so are inefficient. Why is this?

Answer 21

1. Activation of a single synapse will produce little effect
2. NMDA (gluR) receptor channels remain blocked by Mg²⁺ so don’t activate post-synaptic membrane
3. If this happens a lot, then the synapse is probably not doing anything useful

Question 22

If many synapses activate simultaneously, what happens then?

Answer 22

-> Postsynaptic depolarisation -> NMDA receptors unblock and allow Ca²⁺ entry at active synapses

Question 23

What synapse-strengthening processes does increased [Ca²⁺]_in trigger?

Answer 23

• Inc number of AMPA receptors
• Inc effectiveness of AMPA receptors (phosphorylation)
• Inc size of dendritic spine
• Inc size of axon bouton (via retrograde signals)

Lead to an effective synapse, whilst those that aren’t acive at the same time as many others will shrink.

Question 24

What is meant by synaptic plasticity in infants?

Answer 24

Each brain area/pathway has a unique “critical period” after birth, when it is still plastic so brains of babies can adapt to abnormal situations.