Development of CNS and anomalies Flashcards
Describe the stages of prenatal development of the CNS.
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
What is the main risk of development during the first 26 days?
Mother may not be aware of the pregnancy and so external factors may affect initial development e.g. stress, drugs, infection, nutrition
Describe the stages of postnatal development of the CNS.
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
At what age does the loss of neurons begin?
As the brain reaches maturity around 20 years of age. But synaptic processes continue to improve throughout life.
From which layer of embryonic tissue do neurons arise? What else does this layer form?
From ectoderm layer following gastrulation of epiblast. Ectoderm forms the nervous system and skin
What does neurulation cause?
Neurulation within the ectoderm forms the neural plate from which all the nervous system forms.
What type of signals are received that induce neurulation and where are they from?
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.
What processes are involved in the folding of the neural plate into folds and grooves?
Changes in cell shape
Movement of cells
Interactions with surrounding tissue
What happens as the neural plate folds?
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.
What type of neurons are formed from the neural crest cells?
Neurons with cell bodies in PNS e.g. sensory neurons, postganglionic autonomic and schwann cells
What happens to the notochord?
Lost to the vertebral column contributing to the nucleus pulposis of intervertebral discs.
What will result from a defective closure of the neural tube anteriorly?
Anecephaly - lack of extensive fore and midbrain.
Low survival rate
What will result from a defective closure of the neural tube posteriorly?
Spina bifida
What causes defective closure of the neural tube?
Folic acid deficiency and gene defects affecting the cell-cell interactions and surface protein production.
How do neurons become organised?
Anterior-posterior patterning + Dorsal-ventral patterning + medial-lateral patterning = 3D plan for the location of nuclei
What determines polarity of the neural tube?
Signals from cell surface interactions of signals
What determines anterior-posterior patterning?
DICKKOPF - For anteriorisation of the 3 vesicles with all the brain deriving froms its wall.
NOGGIN
What does the overexpression of Dickkopf lead to?
Enlarged heaf
What vitamin affects forebrain development and why?
VIT. A - interferes with the RETANOIC ACID signalling pathway
What is the neural tube filled with?
Fluid in its canal
What determines dorsal-ventral patterning?
Shh (Sonic hegehog).
Highest concentrations at base of brain on ventral side.
What does ventral development determine?
Motor neurons of CN, dopaminergic neurons, serotonergic neurons
What is the loss of dopaminergic and serotonergic neurons linked to?
Dopamine loss = PD
Serotonin loss - Psychiatric disorders and clinical depression
What is cortical layering?
The organisation within the nuclei to form 6 layers.
Proliferation —> Migration —> Differentiation
Which is the most dense cortical layer?
4th
What happens during the proliferation phase of cortical layering?
The ventricular zone lining the neural tube produces cortical neuroblasts at 5-20wks
If a problem arises during the proliferation phase of cortical layering, where does it affect?
The cortex
What happens during the migration phase of cortical layering?
Radial glia provide a scaffold for the neuroblasts to migrate along for inside-out layering as post-mitotic immature neurons.
Which cortical layer forms first and how does it continue to develop?
The 1st layer forms and subsequent neurons form over the top. The most outer layer is formed last
When will the neurons mature and differentiate?
Once migration is complete.
Must be within the right layer for its function as cell bodies and neuron length vary
What is cortical dysgenesis?
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
What is Liss encephaly?
A brain with a smooth cortex/no folds and disorganised layers causing intellectual impairment.
What happens during the differentiation phase of cortical layering?
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
How does an axon form an appropriate connection?
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.
Give examples of chemoattractants and chemorepellants used in axon migration.
Netrin, eptrin
What is the axon and growth cone composed of?
Axon = microtubules
Growth cone = F-actin
What forms a white matter tract?
Axons grow together and bundle during fasciculation/arrangement. The axons are joint by CAMs. The tracts move together along the molecular highway.
What must occur for synpatogenesis?
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.
What results from a low level of NGF?
Synapses disconnect
What happens during pruning?
Synapses are lost to apoptosis to refine the connections. This mainly happens in the embryo and allows for neuroplasticity, under gene expression control.
