Development and Anomalies of Development of the CNS Flashcards
List 5 key events that occur in prenatal development of the brain.
For each event, give an approximation of the time at which they occur after conception.
3 weeks: First neurones are born.
6 weeks: Cortical neurones begin to migrate.
9 weeks: Midbrain expands.
12 weeks: Cerebellum is visible.
6-9 months: Most major nerve tracts formed.
List 5 key events that occur in postnatal development of the brain.
For each event, give an approximation of the time at which they occur after conception.
12 months: Majority of proliferation is complete.
18 months: Myelination is 50% complete.
<3 years: Number of synapses increases.
> 3 years: Number of synapses begins to decline in a process known as pruning.
20 years: Brain is mature in gross structure.
What is gastrulation?
What is a gastrula?
- The transformation of a blastula into a gastrula.
- A gastrula is a polarised ball of stem cells consisting of 3 layers (the endoderm, mesoderm and ectoderm).
What are the fates of the layers of a gastrula?
- The endoderm is the precursor for viscera.
- The mesoderm is the precursor for musculoskeletal systems.
- The ectoderm is the precursor for the nervous system and skin.
What is the neural plate?
The section of the ectoderm from which the nervous system is formed.
What is neural induction?
On which embryological structures does neural induction rely?
- The process by which embryonic cells in the ectoderm acquire a fate to form the neural plate rather than give rise to other structures such as the skin.
- Neural induction relies on both the ectoderm and the notochord.
What is neurulation?
When does neurulation begin?
- The transformation of the neural plate into the neural tube by folding, invaginating and closing.
- This occurs at 3 weeks after conception.
What is the neural crest?
From which cells does the neural crest originate?
- Patches of cells adjacent to the neural tube that appear after neurulation.
- These are the cells that were on the boundary that separated the neural plate from the rest of the ectoderm before neurulation.
What is the fate of the neural crest?
The neural crest will form:
1 - All neurones with cell bodies in the peripheral nervous system.
2 - All Schwann cells.
In which direction does the closure of the neural tube (after invagination of the neural plate) occur during neurulation?
From posterior to anterior.
List 2 defects that arise from defective closure of the neural tube.
For each defect, state whether the defect is on the anterior or posterior side of the neural tube.
1 - Anencephaly (anterior).
2 - Spina bifida (posterior).
Define anencephaly.
Absence of a major portion of the brain.
Why is folic acid important for foetal development?
Because folic acid is required for nucleic acid production, and therefore cell division, which occurs very frequently during foetal development.
Define rostral and caudal.
- Rostral refers to the anterior aspect of the head.
- Caudal refers to the posterior aspect of the head.
What determines anterior-posterior and dorsal-ventral patterning of the neural tube to enable cells to function in the correct 3D location?
- Genes produce signals for polarity, which are secreted and interact with cell surfaces.
- E.g. The dickkopf and noggin genes produce signals for anterior expression. Cells expressing these genes will therefore be found in the forebrain.
- E.g. The sonic hedgehog gene produces signals for ventral expression.
List 3 cells expressed by ventral neural tissue.
1 - Cranial nerves.
2 - Dopaminergic neurones.
3 - Serotonergic neurones.
Why is vitamin A contraindicated with pregnancy?
Because vitamin A can disrupt anterior-posterior patterning of the neural tube, leading to poor forebrain development.
When and where are cortical neuroblasts formed?
- From 5-20 weeks after conception.
- In the ventricular zone which lines the inner neural tube.
Which genes are responsible for the proliferation of cortical neuroblasts?
Uniquely human genes.
What might result from an abnormality in cortical neuroblast proliferation?
What might cause such an abnormality?
- Microcephaly.
- Zika virus might impair neuroblast proliferation.
What determines the organisation of cells within the cortex of the brain once polarity has been established?
Inside-out layering:
1 - Radial glia span the length of the cortical plate (the area that will form the cortex), giving them a spoke-like radial appearance.
2 - Radial glia form scaffolding across the cortical plate.
3 - Cortical neuroblasts are formed at the ventricular zone, which lies beneath the cortical plate.
4 - The first layer of cortical neuroblasts begin to migrate up the scaffolding of the cortical plate, but only migrate a short distance before stopping.
5 - Subsequent layers of cortical neuroblasts migrate further than previous cortical neuroblasts, forming additional layers from inside to out.
What group of syndromes can arise from abnormalities of cortical neuroblast migration?
Cortical dysgenesis.
What is lissencephaly?
The formation of a smooth cortex due to disorganised layering and deficiencies in neurone production.
List 2 chemoattractants / chemorepellents that are involved in axon guidance.
1 - Netrin.
2 - Ephrin.
Define growth cone.
The structure at the tip of a growing axon that receives signals for axonal guidance.
Define fasciculation.
Describe the process of fasciculation.
- The formation of fascicles in the developing brain, which form white matter tracts in the adult brain.
1 - Fascicles form when multiple axons grow together in the same direction by adhering axons with that of a lead neurone. Adhesion of axons occurs via cell adhesion molecules (CAMs).
2 - The lead neurone’s growth cone guides axonal growth for all neurones adhered to it.
3 - Neurones that grow after the development of fascicles also follow the path of the tract.
Give an example of a neurotrophic factor involved in synaptogenesis.
Nerve growth factor.
What process might be deficient in autism?
Pruning.
What process accompanies the loss of synapses seen with pruning?
Organised apoptosis (not necrosis).
List 6 conditions that are caused by neurodevelopmental abnormalities.
1 - Autism.
2 - Schizophrenia.
3 - Cerebral palsy.
4 - Cerebellar ataxia.
5 - Epilepsy.
6 - Dyslexia.
