02. Neurodevelopment II - Part 1

Question 1

The steps of embryonic brain development:
from neural tube to brain

Answer 1

Neural tube -> brain
1. Cell birth/proliferation
2. Cell migration
3. Cell differentiation and maturation
4. Synaptogenesis and synaptic pruning
5. Cell death
6. Myelination (myelogenesis)

Question 2

STEP 1:
What is cell birth / proliferation?

Answer 2

Neurogenesis and gliogenesis
A huge process (up to 250,000 neurons born per minute)

Question 3

Neurogenesis cell division is…

Answer 3

…not symmetrical. Stem cell -> progenitor cell -> glioblasts and neuroblasts -> glial cells & neurons

Question 4

What is ‘The Brain’s Nursery’?

Answer 4

The ventricular zone

Area of the neural tube where proliferation (non-symmetrical mitosis) takes place

Question 5

Who discovered the ‘Brain’s nursery’?

Answer 5

Santiago y Cajal

Question 6

The neural tube in adults - the hole

Answer 6

The hole in the neural tube in embryos becomes the centre of the spinal cord and the ventricular system (hollow areas in the brain) in adults

Question 7

STEP 2:
What is cell migration?

Answer 7

The movement of newly formed cells towards the outer layers of the brain

Question 8

How does the cortex develop?

Answer 8

Inside-out (across species)

Question 9

How do the neural cells know where to go (during migration)?

Answer 9

A ‘Primitive map’ predisposes cells born in a certain region to migrate to a certain location of the cortex (Rakic et al 2009)

Question 10

How does cell migration occur?

Answer 10

Cells navigate using chemical signals (immunoglobins and cytokines) & ‘climb’ radial glia to move to where they are needed.

Question 11

What are radial glia?

Answer 11

Glial cells that look like wheels and have spokes

Question 12

Where do neurons travel from and to during migration?

Answer 12

Neurons travel from the Ventricular zone (brain’s nursery) to the Marginal zone

Question 13

How do the neurons travel?

Answer 13

They ‘shimmy up’ the radial glia, and migrate from one ‘spoke’ (‘vine’) to another

Question 14

Neural migration in newborn babies

Answer 14

For the first 7 months of life, neurons migrate to the infant frontal lobe. Most of them become inhibitory GABAergic neurons

Question 15

STEP 3:
How does cell differentiation/maturation occur?

Answer 15

Once neurons arrive at their destination, they express genes that let them grow an axon (mm/day) and dendrites (micrometre/day). This gives them a certain shape and makes them a certain type of neuron.

Question 16

What is dendritic arborisation?

Answer 16

‘Branching’ & growth of dendritic spines

Question 17

How do the neurons know what to do?

Answer 17

Cells secrete chemicals, influencing their neighbours (induction)

Question 18

Stem cells are pluripotent (can differentiate into any cell), so can be used for…

Answer 18

Treating Parkinson’s

Question 19

STEP 4:
What is synaptogenesis?

Answer 19

The creation of a synapse

Question 20

STEP 4:
What is synaptic pruning?

Answer 20

The removal of a synapse that isn’t being used

Question 21

How are synapses made?

Answer 21

The growing end of an axon is a ‘growth cone’ (Ramon y Cajal, 1890) which extends by adding microtubules to the end. They also grow ‘filopodia’, which feel around for the destination. Growth cones are attracted to chemicals from target sites (Roger Sperry, 1943) - e.g. Cell adhesion molecules (CAMs) & Tropic molecules

Question 22

In synaptogenesis, once contact is made…

Answer 22

Axon and target cause each other to make proteins allowing them to attach and form a synapse (postsynaptic density proteins)

Question 23

Synapses are very … when they are first formed

Answer 23

Slow (but they speed up with time)

Question 24

How do filopodia ‘feel around’

Answer 24

They can make physical contact with other cells (contact guidance) or they can be chemically guided (chemotropism) - they have protein receptors on their membrane that ’recognise’ various molecules

Question 25

Synaptic pruning

Answer 25

Synapses often used are strengthened, and synapses that aren't used are eliminated. AKA 'neural plasticity'

Question 26

When does synaptic pruning occur a lot?

Answer 26

Adolescence (Powell, 2006). The process is completed earlier in girls than boys

Question 27

STEP 5: What is cell death?

Answer 27

Infants have a period many cells die (via apoptosis). First noticed by Viktor Hamburger(1900-2001)

Question 28

Apoptosis causes the separation of fingers via...

Answer 28

The apoptosis of webbing between them

Question 29

Apoptosis vs necrosis

Answer 29

Apoptosis: active and deliberate Necrosis: happens after injury, causes damage to surrounding cells

Question 30

To avoid apoptosis and survive, a neuron will need:

Answer 30

A) neurotrophins (growth factors) from its target cells B) active communication with other neurons which leads to the strengthening of the synapses (D.O. Hebb)

Question 31

STEP 6: What is myelination (myelogenesis)

Answer 31

Glial cells from a fatty sheath over axons, speeding up saltatory conduction by preventing signal leakage

Question 32

Myelination in the PNS

Answer 32

Uses Schwann cells -> they only myelinate one axon

Question 33

Myelination in the CNS

Answer 33

Uses oligodendrocytes -> they myelinate many axons