Development and Anomalies of the Development of the CNS Flashcards
List the timings of major events in human brain development
- 22-26 days
- 6 weeks
- 9 weeks
- 12 weeks
- 6-9 months
- 12 months
- 3-4 years
- 20 years
- 20 years +
- 22-26 days = first neurones born (development sensitive to environment e.g. nutrition, infection, exposure
- 6 weeks = cortical neurones migrate
- 9 weeks = midbrain expands considerably
- 12 weeks = cerebellum is visible
- 6-9 months = most major nerve tracts formed
- 12 months = neurone proliferation complete
- 3-4 years = myelination 50% complete
- 20 years = brain is mature in structure
- 20 years + = dynamic processes continue
Describe briefly the process of gastrulation
ball of cells --> polarised so head and tail discernible 3 layers: - endoderm --> viscera - mesoderm --> musculoskeletal systems - ectoderm --> nervous system and skin
When does neurulation occur?
3 weeks post conception
Describe the process of neurulation
How is it controlled?
Ectoderm –> neural induction –> neural plate
- cell-cell interactions between mesoderm and notochord, cell surface proteins detect signals from notochord
Neural fold form. This involves:
- changes in cell shape
- movement of cells
- interactions with surrounding tissue
Neural fold fuse –> neural tube –> all CNS
Neural tube zips from tail to head
Neural crest cells –> neurones with cell bodies in the PNS e.g. adrenal medulla, sensory neurones, post ganglionic neurones
Clinical relevance of neurulation:
- What is the result of an anterior defective closure?
- What is the result of a posterior defective closure?
anterior –> anencephaly, no extensive forebrain/midbrain
posterior –> spina bifida
What are the causes of neural tube defects? x2
folic acid required for massive cell division
gene defects can affect cell-cell interactions
What is anterior-posterior patterning?
3 vesicles at anterior end of neural tube, all brain is derived from the walls of these
Signals for polarity include:
- secreted and cell surface interactions
e.g. dickkopf (fathead) and noggin = anteriorising
forebrain and too much Vit A is teratogenic (signalling pathways require retinoid acid)
What controls dorsal-ventral patterning?
Ventral expression of Sonic hedgehog (Shh) gene
At the base of the brain
Leads to development of motor neurones of cranial nerves, dopaminergic neurones and serotonergic neurones
What three things determine the basic plan for the 3D location of nuclei?
anterior-posterior axis
dorsal-ventral axis
lateral-medial axis
How many layers are there in the neocortex?
How to the layers vary?
Which is the densest layer?
6 layers in neocortex
Vary in cell size and shape
4 is the most dense
What are the basic 3 steps of cortical layering?
- proliferation
- migration
- differentiation
Describe proliferation (first step of cortical layering)
the ventricular zone
the cells that line the fluid filled ventricles proliferate the most
cortical neuroblasts born weeks 5-20 (don’t look like neurones yet)
Describe migration (second step of cortical layering)
- radial glia provide the scaffolding (only present in developing brain)
- post mitotic immature neurones migrate up from ventricular zone along radial glia
- each cells ‘hops’ over the one before it in the cortical plate –> leads to layering
What is cortical disgenesis?
What can it lead to?
The interruption of migration and therefore a defect in cortical layering
25+ human syndromes with defective migration
e.g. lissencephaly, epilepsy, autism, dyslexia, schizophrenia, down’s syndrome
What is lissencephaly?
An example of cortical diagenesis
Results in a smooth cortex (very few sulci)
Intelectual disability
Describe differentiation (third step of cortical layering)
immature neurones differentiate - extensive dendritic processes - axons - no further division Differential gene activation - transmitters/receptors and ion channels
Describe how neurones are able to make appropriate connections
Axons need to extend and grow towards correct target
- they do this with growth cones which interact with the environment
- chemoattractants and chemorepellants e.g. nitric, ephori
- axon receptor expression (proteins)
Axons need to extend and grow towards correct targets
- they do this via a process called fasciculation which leads to white matter tracts
- via CAMs that stick axons together
- molecular highways provide routes for axons to follow
Describe synaptogenesis
Two-way signalling process (like neuronal speed dating!)
Neurotrophic factors eg. NGF (neuronal growth factor)
These signals remain in adulthood, but may deplete in diseases such as depression which leads to loss of synapses
What is refinement?
Some synapses are made and then lost - pruning
Neuronal cell death via apoptosis (controlled)
also occurs pathologically e.g. AD and PD
controlled by gene expression
Name some neurodevelopment disorders A S C p C a E D
Autism Schizophrenia Cerebral Palsy Cerebral Ataxia Epilepsy Dyslexia
What is the therapeutic relevance of neurodevelopment?
stem cells in adults? –> reactive development process in the adult brain
spinal damage
cell transplant for neurodegenerative disease
