Week 1

Question 1

Timing of major events in human brain development

Answer 1

Prenatal:
-22-26 days- first neurones born
-6 weeks- cortical neurons migrate
-9 weeks- midbrain expands considerably
-12 weeks- cerebellum is visible
-6-9 months- most major nerve tracts formed
Postnatal:
-12 months- majority neuron proliferation complete
-18 months- myelination 50% complete
-<3 years- increasing number synapses
-20 years- brain is mature in structure
-20+ years- dynamic processes continue

Question 2

What are the key processes

Answer 2

How do some cells end up as neurones
How do they become organised in the developing brain
How do they make appropriate connections with eachother

Question 3

How do some cells end up as neurones

Answer 3

Gastrulation (polarised ball of cells)- head and tail discernible
-3 layers
-ectoderm: nervous system (skin)
-mesoderm
-endoderm

Question 4

Neurulation

Answer 4

3 weeks post conception
-ectoderm
—neural induction
—neural plate- whole nervous system
Formation of the neural plate
-cell to cell interactions: mesoderm and notochord, cell surface proteins
Extracellularly secreted molecules
Involves:
-changes in cell shape
-movement of cells
-interactions with surrounding tissue
Neural folds fuse -> neural tube- all the CNS
Neural crest-> neurones with cell bodies in PNS, sensory, post ganglionic ANS
-Schwann cells

Question 5

Clinical relevance of neurulation

Answer 5

Defective closure of the neural tube
-anteriorly: anencephaly
-posteriorly: spina bifida
Cause:
-massive cell division- dependent on folic acid
-gene defects- cell to cell interaction

Question 6

How do neurones become organised in the developing brain
Anterior-posterior patterning

Answer 6

Anterior end
-3 vesicles forebrain, midbrain, hindbrain
-all brain derived from walls
Signals for polarity:
-secreted and cell surface interactions
-dickkopf and noggin= anteriorising
-forebrain and vitamin A: (retinoic acid) taking a large amount can interfere with anteriorising interactions can affect the forebrain

Question 7

How do neurones become organised in the developing brain
Dorsal ventral patterning

Answer 7

Sonic hedgehog (Shh)
-ventral expression :more highly expressed
—motor neurones of CN
—Dopaminergic neurones -PD?
—serotonergic neurones- psychiatric disorders
Basic plan determined by
-AP axis and DV axis and ML axis -3D location- nuclei

Question 8

Cortical layering

Answer 8

(Neo) cortical layer
Neurones grey matter-neocortex neurones internal organisation
Myelinated axons white matter
Proliferation:
-ventricular zone
-cortical neuroblasts born weeks 5-20 weeks
—250000 per minute any interruption affects production cortical neurones
Abnormality: microencephaly not enough (Zila virus), macroencephaly too many
Migration:
-radial glia provide scaffolding
Differentiation

Question 9

Inside out layering

Answer 9

Lateral ventricle- ventricular zone- cortical plate
Post mitotic immature neurones move up over eachother, oldest layer on inside nearest ventricular zone
Form glia generally dont find in adult, radial glia, problem with rebuilding adult brain

Question 10

Cortical layering migration abnormalities

Answer 10

Cortical dysgenesis:
-25+ human syndromes with defective cortical migration
-differing degrees of affect
Lissencephaly: extreme example
-smooth cortex
-disorganised layers
-no gyri at all
-profound implications

Question 11

Cortical layering differentiation

Answer 11

At final destination
Differentiate— neurones
-cellular structure
-no further division
-differential gene activation
—transmitters/receptors
—ion channels

Question 12

Making appropriate connections

Answer 12

Axons need to
-extend and grow towards correct targets= axon guidance
-growth cones
—chemoattractants (if coming from mutated genes- problem) and chemorepellents
—eg netrin and ephrin can change direction growing in
-grow together =fasciculation
—white matter tracts
Via CAMs (cell adhesion molecules) = molecular highways

Question 13

Synaptogenesis

Answer 13

Two way signalling critical. Repair brain need to understand this process otherwise synapses disappear
-presynaptic <-> postsynaptic neurone
-neurotrophic factors : Eg NGF (nerve growth factor)

Question 14

Refinement

Answer 14

Some synapses lost= pruning
Neuronal cell death
-organised (apoptosis) not necrosis controlled by gene expression
-also occurs pathologically
-eg AD, PD, therapeutic intervention

Question 15

CNS development is complex

Answer 15

Carefully controlled by precisely timed gene expression
Potential to go wrong
-mutations
-environment

Question 16

Conditions with a neurodevelopmental aspect

Answer 16

Autism, cerebellar ataxia, cerebral palsy, dyslexia, epilepsy, schizophrenia

Question 17

Therapeutic relevance

Answer 17

Can these processes be seen in the adult brain
Neuroplasticity
Stem cells in adults
-> CNS repair?
-spinal cord damage
-neurodegenerative diseases