Development of CNS and anomalies

Question 1

Describe the stages of prenatal development of the CNS.

Answer 1

22-26 days: First neurons born
6wks: Cortical neurons migrate to cortex
9wks: Cerebellum visible
6-9mnths: Major nerve tracts form = white matter but no connections

Question 2

What is the main risk of development during the first 26 days?

Answer 2

Mother may not be aware of the pregnancy and so external factors may affect initial development e.g. stress, drugs, infection, nutrition

Question 3

Describe the stages of postnatal development of the CNS.

Answer 3

12mnths: Neuron proliferation complete but retains capacity to produce new
18mnths: 50% of myelination complete
3-4yrs: Visual system connections complete
Teens: Myelination complete
20yrs+: Mature structure and dynamic processes occur

Question 4

At what age does the loss of neurons begin?

Answer 4

As the brain reaches maturity around 20 years of age. But synaptic processes continue to improve throughout life.

Question 5

From which layer of embryonic tissue do neurons arise? What else does this layer form?

Answer 5

From ectoderm layer following gastrulation of epiblast. Ectoderm forms the nervous system and skin

Question 6

What does neurulation cause?

Answer 6

Neurulation within the ectoderm forms the neural plate from which all the nervous system forms.

Question 7

What type of signals are received that induce neurulation and where are they from?

Answer 7

Direct signal from notocord to ectoderm causing direct cell-cell interations with cell proteins or proteins within the environment.
May also be extracellularly secreted molecules that produce a gradient. The area of highest concentration becomes the neural plate.

Question 8

What processes are involved in the folding of the neural plate into folds and grooves?

Answer 8

Changes in cell shape
Movement of cells
Interactions with surrounding tissue

Question 9

What happens as the neural plate folds?

Answer 9

The folds fuse together from caudal to rostral to release the groove and form the neural tube which forms all of the CNS. The remaining fused ectoderm forms the skin. The neural crest cells released become all the neurons with cell bodies in PNS.

Question 10

What type of neurons are formed from the neural crest cells?

Answer 10

Neurons with cell bodies in PNS e.g. sensory neurons, postganglionic autonomic and schwann cells

Question 11

What happens to the notochord?

Answer 11

Lost to the vertebral column contributing to the nucleus pulposis of intervertebral discs.

Question 12

What will result from a defective closure of the neural tube anteriorly?

Answer 12

Anecephaly - lack of extensive fore and midbrain.

Low survival rate

Question 13

What will result from a defective closure of the neural tube posteriorly?

Answer 13

Spina bifida

Question 14

What causes defective closure of the neural tube?

Answer 14

Folic acid deficiency and gene defects affecting the cell-cell interactions and surface protein production.

Question 15

How do neurons become organised?

Answer 15

Anterior-posterior patterning + Dorsal-ventral patterning + medial-lateral patterning = 3D plan for the location of nuclei

Question 16

What determines polarity of the neural tube?

Answer 16

Signals from cell surface interactions of signals

Question 17

What determines anterior-posterior patterning?

Answer 17

DICKKOPF - For anteriorisation of the 3 vesicles with all the brain deriving froms its wall.
NOGGIN

Question 18

What does the overexpression of Dickkopf lead to?

Answer 18

Enlarged heaf

Question 19

What vitamin affects forebrain development and why?

Answer 19

VIT. A - interferes with the RETANOIC ACID signalling pathway

Question 20

What is the neural tube filled with?

Answer 20

Fluid in its canal

Question 21

What determines dorsal-ventral patterning?

Answer 21

Shh (Sonic hegehog).

Highest concentrations at base of brain on ventral side.

Question 22

What does ventral development determine?

Answer 22

Motor neurons of CN, dopaminergic neurons, serotonergic neurons

Question 23

What is the loss of dopaminergic and serotonergic neurons linked to?

Answer 23

Dopamine loss = PD

Serotonin loss - Psychiatric disorders and clinical depression

Question 24

What is cortical layering?

Answer 24

The organisation within the nuclei to form 6 layers.

Proliferation —> Migration —> Differentiation

Question 25

Which is the most dense cortical layer?

Answer 25

4th

Question 26

What happens during the proliferation phase of cortical layering?

Answer 26

The ventricular zone lining the neural tube produces cortical neuroblasts at 5-20wks

Question 27

If a problem arises during the proliferation phase of cortical layering, where does it affect?

Answer 27

The cortex

Question 28

What happens during the migration phase of cortical layering?

Answer 28

Radial glia provide a scaffold for the neuroblasts to migrate along for inside-out layering as post-mitotic immature neurons.

Question 29

Which cortical layer forms first and how does it continue to develop?

Answer 29

The 1st layer forms and subsequent neurons form over the top. The most outer layer is formed last

Question 30

When will the neurons mature and differentiate?

Answer 30

Once migration is complete.

Must be within the right layer for its function as cell bodies and neuron length vary

Question 31

What is cortical dysgenesis?

Answer 31

A defective cortical migration that can cause a spectrum of syndromes e.g. epilepsy, schizophrenia, autism, dyslexia, cerebral palsy.
Can be present in a normal functioning brain

Question 32

What is Liss encephaly?

Answer 32

A brain with a smooth cortex/no folds and disorganised layers causing intellectual impairment.

Question 33

What happens during the differentiation phase of cortical layering?

Answer 33

Differentiate after migration to determine transmitters, receptors and ion channels through gene activation. There is extensive sprouting and axon growth. Now POST-MITOTIC so no further division

Question 34

How does an axon form an appropriate connection?

Answer 34

Axons extend and grow towards its target with axon guidance.
Growth cones at the end of the sprouting neuron look for chemoattractants and chemorepellants to decide where to migrate and make a connection. The axons receptor expression determines the attractants and route followed.

Question 35

Give examples of chemoattractants and chemorepellants used in axon migration.

Answer 35

Netrin, eptrin

Question 36

What is the axon and growth cone composed of?

Answer 36

Axon = microtubules

Growth cone = F-actin

Question 37

What forms a white matter tract?

Answer 37

Axons grow together and bundle during fasciculation/arrangement. The axons are joint by CAMs. The tracts move together along the molecular highway.

Question 38

What must occur for synpatogenesis?

Answer 38

Two way signalling between the pre and posy synaptic neuron.
Both neurons must release tropic factors e.g. NGF to interact and form a synapse.
If one doesn’t respond the axon moves on.

Question 39

What results from a low level of NGF?

Answer 39

Synapses disconnect

Question 40

What happens during pruning?

Answer 40

Synapses are lost to apoptosis to refine the connections. This mainly happens in the embryo and allows for neuroplasticity, under gene expression control.