Development of the CNS part 2 Flashcards
Where does the brain form from
The most anterior part of the neural tube
- Around 4 weeks, you get differentiation of the wall of the anterior neural tube to form three primary vesicles. Name these primary vesicles.
Prosencephalon – future forebrain
Mesencephalon – future midbrain
Rhombencephalon – future hindbrain
Below the rhombencephalon you will see the spinal cord
- Describe the changes that occur to these three vesicles in the week or so following their formation. i.e the 5th week of development
The first and third vesicles divide in two
Prosencephalon telencephalon + diencephalon
Rhombencephalon pons + medulla
Midbrain stays as it is
What are the telencephalon and diencephalon
Telencephalon: cortex
Diencephalon: thalamus and hypothalamus
How many vesicles are seen in the developing brain
Only the anterior portion of the neural tube develops into the brain.
Three primary vesicles form:
o Prosencephalon – future forebrain.
o Mesencephalon – future midbrain.
o Rhombencephalon – future hindbrain.
Over the next week, the most superior vesicle divides in two and the third (inferior) vesicle divides into two.
o This produces 5 secondary vesicles.
As the brain continues to develop, what will each region become
The telencephalon will become the cerebral hemispheres.
Less expansion occurs in the lower portion of the developing forebrain as this becomes the diencephalon (thalamus, hypothalamus, epithalamus and subthalamus).
Developing hindbrain divides into the pons and medulla.
- What important structure begins to appear quite late in development (around 8 weeks) and where does it appear from?
Cerebellum – appears as an out pouching from the back of the pons
Summarise the development of the brain regions at approximately 8 weeks
As development continues, the neural tube proliferates more and more.
The space within the neural tube (central canal) becomes smaller relative to the wall and this becomes the ventricular system.
The development of the cerebellum also begins – an out-pouching from the back of the pons.
Summarise the folding of the brain
picture is approx. 4, 5 and 8 weeks.
The vesicles aren’t in a straight line, there are 3 flexures.
o Named based on position of the flexures.
Cephalic flexure (brain)
Pontine flexure (pons)
Cervical flexure (cervical spine)
o The flexures become more and more exaggerated upon development.
What do the flexures split the brain into
Define the levels of the brain based on their embryonic development
cephalic, pontine and cervical flexures divide into prosencephalon, mesencephalon and rhombencephalon
When can we see the individual hemispheres
At around 8 weeks
What changes are still being made in the brain at term (i.e when the baby is born)
Myelination of all the pathways in the brain- setting up pathways to stand up and perform tasks
Whereas other animals can stand upon birth.
What does the telencephalon contain
The forebrain situated rostral to the optic vesicles becomes the telencephalon and contains:
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Cerebral cortex
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Commissures – made up of cortico-cortical connections
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Basal ganglia – which develop as swellings that protrude into the cavity of the lateral ventricles, along with the developing hippocampus.
Describe the expansion of the telencephalon during development
The telencephalon (hemispheres) expands much more than the other parts of the brain and ultimately covers the diencephalon and midbrain. The two swellings meet in the midline, trapping a small amount of mesenchymal tissue which forms the falx cerebri. Similarly, the occipital lobes of the hemispheres are separated from the cerebellum by mesenchyme (which becomes the tentorium cerebelli).
Describe the development of sulci and gyri
Grooves gradually appear on the smooth surface of the hemispheres and become the sulci. The gyri thus formed allow a much greater volume of cortex (folded up) to be packed into the cranium. The cortex that covers part of the corpus striatum (lentiform nucleus) is called the insula. It remains fixed while the temporal, parietal and frontal lobes grow rapidly to bury it within the lateral sulcus.
Summarise how the ventricular system is formed in the developing brain
This bending and folding of the developing brain diminish or enlarge the different regions of the lumen enclosed by the developing neural tube. These lumenal spaces eventually become the ventricular system of the mature brain.
Describe the formation of the fourth ventricle
In the neural tube in the region that will become the brainstem, the roof plate rapidly proliferates and causes the alar plates to split apart so that they are lateral to the roof plate
The space left from the proliferation of the roof plate will become the 4th ventricle
Summarise cortical development
Cortical development: neuroblasts formed from neuroepithelium migrate towards pial surface along radial glia, with successive waves forming the cortical layers; myelination occurs gradually to term and beyond; produces 6 discrete layers of cells - forming the cortex
Radial glial cells: astroglia that develop vertically to act as scaffolding to reach pial surface from ventricles
- How do neuroblasts migrate from the inner membrane to the outer membrane in the brain?
They attach themselves to radial glial cells and climb up them towards the outer membrane
Radial glial cells have their cell bodies anchored to the inner membrane and have a single long process to the outer membrane
Describe the development of the cortex
The brain has a core of white matter with grey matter on the outside.
o Grey matter = nuclei that have migrated from the inner membrane of the neural tube.
Neuroblasts proliferate at the inner membrane.
o Some neuroblasts will stay in the middle and form basal ganglia.
o Some neurones then migrate towards the outer membrane.
Migration occurs by neuroblasts attaching themselves to radial glial cells – these cells have their soma attached to the inner membrane and have a single long process to the outer membrane.
The neurones then climb towards the outer membrane.
These proliferations and migrations occur in waves to form layers of the cortex (1st, 2nd, etc.) until you reach 6 layers – each layer is unique.
What makes us human
the cortex
we are gyricencephalic animals
rodents are lissencephalic
Where are the developmental cells found
In the sub-ventricular zone (ependymal zone)
Describe the importance of the radial glial cells
Vertically orientated from ventricle to pial surface- provide scaffolding for developing neuroblast
Still developing cells in the sub-ventricular zone in the adult brain.
Using soup of growth factors, neurones start migrating and differentiating along neuroglia- in and inside out manner
Different layers have different functions- project. fibres to other regions or local circuits.
helps to ensure the guidance of newly-formed neurones past already generated neurones in the developing nervous system
upon reaching the cortical surface, the neurone will contact the end feet of the radial glial cells and disengage from the glial surface
Describe the direction of migration in the cerebellum
Reversed as opposed to the cortex
The precursors for cerebellar granulae cells are actually on the cerebellar surface, and the processes of Bergmann glia guide postmiotic granule cells past the already generated purkinjie cells into the nascent internal granule layer
What are the six layers (from inside out)
Ventricular zone Sub-ventiruclar zone Intermediate zone Cortical plate Marginal zone Pial surface
At which stage of pregnancy do developmental disorders normally relate to
The 3rd trimester
What does normal development depend on, and summarise what factors can interfere with normal development
Normal development depends on the coordinated completion of several complex processes (e.g. proliferation, differentiation, migration, axon growth and synapse formation)
Genetic mutation and environmental factors such as the mother’s lifestyle, diet and teratogens can interfere with these processes
Where can abnormal development of the neural tube occur
At the top or at the bottom
Summarise the pathogenesis of neural tube defects
Neural tube defects are caused by varying degrees of failure of fusion of the posterior neural arch. The pathogenesis of the disorders is thought to be due to a mixture of:
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Environmental factors – folic acid (folate) taken at the time of conception and in the first trimester of pregnancy reduces the incidence of neural tube defects. Other factors have not been proved, but it is interesting to note that the incidence in the UK is 10 times higher than in Japan, despite comparable education about the importance of folate supplements.
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Genetic factors – subsequent children born to a mother with an affected child have a 10-fold increased risk, but in monozygotic twins rarely are both affected
Describe anencephaly
Anencephaly represents failure of fusion at the cephalic end of the neural tube. Almost no forebrain structures develop, usually with absence of the skull vault. This condition is not compatible with long-term survival.
Describe encephalocele
Herniation of the brain and meninges
Describe craniochischisis
Completely open brain and spinal cord
Describe iniencephaly
Occipital skull and spine defects with extreme retroflex n of the head
Describe spina bifida oculta
Closed asymptomatic neural tube defect in which some of the vertebrae are not completely closed
The lumbosacral site is most common (80%). Spina bifida is caused by local defects in the development and closure of the neural tube and vertebral arches. The main types are shown in Figure 2.9. Deficiency of the meninges in these patients predisposes to meningitis. Bladder problems are also common due to a partial cauda equina syndrome
deficient dura
Describe closed spinal dysraphism
Deficiency of at least two vertebral arches, here covered with lipoma (fat-filled)
Describe meningocele
Protrusion of the meninges (filled with CSF) through a defect in the skull or spine
Describe myelomeningocele
Open spinal cord (with a meningeal cyst)
Protrusion of meninges and spinal cord
What can a deficiency in folic acid during pregnancy lead to
Spinal bifida
Summarise the potential to utilise developmental neurobiology therapeutically
How to replace lost neurone – regulate stem cell differentiation.
How to induce CNS regeneration - guidance mechanisms for axons.
Population of stem cell neurones in the hippocampus- but the brain does not have the capacity or programming to enhance these neurones to replace lost or damaged neurones.
Is a big brain everything?
No
As apoptosis of neurones is essential during development of brain- and the absence of this process is indicative of abnormal development and thus a loss of connectivity between different neurones.
However, the brain does atrophy in neurodegenerative disease
Describe the inside-out migration of cells in the cortex
Each layers consist of a cohort of cells ‘born’- and which therefore undergo their terminal divisions- at a distinct time.
The firstborn cells are located in the deepest layers, later generations migrate radially from their site of final division in the ventricular zone, travelling through the older cells coming to lie superficial before them.
these differences in time of cell origin are matched by differences in gene expression in distinct cohort of cells.
