Development of the CNS part 2

Question 1

Where does the brain form from

Answer 1

The most anterior part of the neural tube

Question 2

18. Around 4 weeks, you get differentiation of the wall of the anterior neural tube to form three primary vesicles. Name these primary vesicles.

Answer 2

Prosencephalon – future forebrain
Mesencephalon – future midbrain
Rhombencephalon – future hindbrain
Below the rhombencephalon you will see the spinal cord

Question 3

19. Describe the changes that occur to these three vesicles in the week or so following their formation. i.e the 5th week of development

Answer 3

The first and third vesicles divide in two
Prosencephalon  telencephalon + diencephalon
Rhombencephalon  pons + medulla
Midbrain stays as it is

Question 4

What are the telencephalon and diencephalon

Answer 4

Telencephalon: cortex
Diencephalon: thalamus and hypothalamus

Question 5

How many vesicles are seen in the developing brain

Answer 5

 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.

Question 6

As the brain continues to develop, what will each region become

Answer 6

 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.

Question 7

20. What important structure begins to appear quite late in development (around 8 weeks) and where does it appear from?

Answer 7

Cerebellum – appears as an out pouching from the back of the pons

Question 8

Summarise the development of the brain regions at approximately 8 weeks

Answer 8

 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.

Question 9

Summarise the folding of the brain

Answer 9

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.

Question 10

What do the flexures split the brain into

Answer 10

Define the levels of the brain based on their embryonic development
cephalic, pontine and cervical flexures divide into prosencephalon, mesencephalon and rhombencephalon

Question 11

When can we see the individual hemispheres

Answer 11

At around 8 weeks

Question 12

What changes are still being made in the brain at term (i.e when the baby is born)

Answer 12

Myelination of all the pathways in the brain- setting up pathways to stand up and perform tasks
Whereas other animals can stand upon birth.

Question 13

What does the telencephalon contain

Answer 13

The forebrain situated rostral to the optic vesicles becomes the telencephalon and contains:
•
Cerebral cortex
•
Commissures – made up of cortico-cortical connections
•
Basal ganglia – which develop as swellings that protrude into the cavity of the lateral ventricles, along with the developing hippocampus.

Question 14

Describe the expansion of the telencephalon during development

Answer 14

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).

Question 15

Describe the development of sulci and gyri

Answer 15

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.

Question 16

Summarise how the ventricular system is formed in the developing brain

Answer 16

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.

Question 17

Describe the formation of the fourth ventricle

Answer 17

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

Question 18

Summarise cortical development

Answer 18

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

Question 19

25. How do neuroblasts migrate from the inner membrane to the outer membrane in the brain?

Answer 19

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

Question 20

Describe the development of the cortex

Answer 20

 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.

Question 21

What makes us human

Answer 21

the cortex
we are gyricencephalic animals
rodents are lissencephalic

Question 22

Where are the developmental cells found

Answer 22

In the sub-ventricular zone (ependymal zone)

Question 23

Describe the importance of the radial glial cells

Answer 23

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

Question 24

Describe the direction of migration in the cerebellum

Answer 24

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

Question 25

What are the six layers (from inside out)

Answer 25

Ventricular zone 
Sub-ventiruclar zone
Intermediate zone
Cortical plate 
Marginal zone
Pial surface

Question 26

At which stage of pregnancy do developmental disorders normally relate to

Answer 26

The 3rd trimester

Question 27

What does normal development depend on, and summarise what factors can interfere with normal development

Answer 27

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

Question 28

Where can abnormal development of the neural tube occur

Answer 28

At the top or at the bottom

Question 29

Summarise the pathogenesis of neural tube defects

Answer 29

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:
•
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.
•
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

Question 30

Describe anencephaly

Answer 30

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.

Question 31

Describe encephalocele

Answer 31

Herniation of the brain and meninges

Question 32

Describe craniochischisis

Answer 32

Completely open brain and spinal cord

Question 33

Describe iniencephaly

Answer 33

Occipital skull and spine defects with extreme retroflex n of the head

Question 34

Describe spina bifida oculta

Answer 34

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

Question 35

Describe closed spinal dysraphism

Answer 35

Deficiency of at least two vertebral arches, here covered with lipoma (fat-filled)

Question 36

Describe meningocele

Answer 36

Protrusion of the meninges (filled with CSF) through a defect in the skull or spine

Question 37

Describe myelomeningocele

Answer 37

Open spinal cord (with a meningeal cyst)

Protrusion of meninges and spinal cord

Question 38

What can a deficiency in folic acid during pregnancy lead to

Answer 38

Spinal bifida

Question 39

Summarise the potential to utilise developmental neurobiology therapeutically

Answer 39

 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.

Question 40

Is a big brain everything?

Answer 40

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

Question 41

Describe the inside-out migration of cells in the cortex

Answer 41

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.