Development of the CNS

Question 1

What is the first thing to happen to the ectoderm around 3 weeks?

Answer 1

There is proliferation of the ectoderm in the midline of the embryonic disc to form the neural plate. This thickens and the neural plate begins to fold on the sides and the two folds fuse to from a tube.

Question 2

What is the wall of the neural tube called?

Answer 2

neuroepithelium

Question 3

What does the neural tube give rise to?

Answer 3

All CNS cells

Question 4

What is the neural canal?

Answer 4

Space in the middle of the neural tube

Question 5

What are neural crest cells?

Answer 5

Cells at the tip of the neural fold

Question 6

What happens to the neural crest cells?

Answer 6

They seperate from the neural tube and don’t take part in the fusion to form the tube - they lie alongside it. You end up with a neural tube and two strips of neural crest tissue one either side.

Question 7

What are the two independent sources of nervous tissue?

Answer 7

neural crest and neural tube

Question 8

What does the neural crest give rise to?

Answer 8

All PNS cells

Question 9

What are the three layers present at the start of development?

Answer 9

endoderm (innermost), mesoderm, ectoderme

Question 10

What is the notochord in the centre at the start of development?

Answer 10

Cartilaginous skeletal rod supporting the body

Question 11

What does the neuroepithelium differentiate into?

Answer 11

Neuroblasts: All neurons with cell bodies in the CNS (includes motor)

Glioblasts: Astrocytes, oligodendrocytes

Ependymal cells: Lining ventricles and central canal. These remain close to the inner membrane of the neural tube and they spread out and form a lining around the developing ventricular system

Question 12

What does the neural crest differentiate into?

Answer 12

• Sensory neurones of dorsal root ganglia and cranial ganglia (not in CNS)
• Postganglionic autonomic neurones
• Schwann cells
• Non-neuronal derivatives e.g. melanocytes

Question 13

What is a common feature of neural crest derived cells?

Answer 13

They are capable of migrating over quite large distances

Question 14

How is the neuroepithelium arranged?

Answer 14

• There is an inner membrane at the bottom and an outer membrane at the top
• Almost all these cells are attached to both the inner and outer membranes - it’s just that the nuclei are in different positions
• The fat cells at the bottom are going through mitosis

Question 15

Describe the differentiation of the neuroepithelium

Answer 15

• Cells withdraw from the outer membrane towards the inner membrane
• They undergo mitosis
• One of the daughter cells will stay attached to the inner cell membrane
• It gets bigger and goes into the cell cycle again
• The other daughter cell migrates away from the inner membrane and then develops into neuroblasts
• They develop processes (one will become the axon)
• These axons are directed away from the inner membrane again
• As this occurs over and over you end up with three layers: mitosis layer (ependymal), cell body layer (grey matter) and axon layer (white matter)
• Leads to formation of grey and white matter

Question 16

Describe glioblast differentiation

Answer 16

• Glioblasts also show a similar pattern of differentiation and migration to neuroblasts
• But glioblasts can migrate into white matter as well
• Remember glioblasts do not develop axons (but do develop processes)

Question 17

What controls differentiation?

Answer 17

• Signalling molecules, secreted by surrounding tissues, interact with receptors on neuroblasts
• Control migration & axonal growth by attraction and repulsion
• Depends on concentration gradient & timing (timing imp as receptors need to exist and some molecules have different effects at different stages of development)

Question 18

What are the layers of the neural tube?

Answer 18

The ependymal layer (surrounds the neural canal), grey matter and white matter

Question 19

What are the roof plates and floor plates?

Answer 19

The roof plate and floor plate are landmarks that show the most dorsal and most ventral parts of the canal

Question 20

Where can signalling molecules be secreted from?

Answer 20

• Secreted either from the tissues surrounding the developing neural tube
• Sometimes secreted by cells within the neural tube

Question 21

Describe the development of the spinal cord

Answer 21

Later on in development the cross section through the neural tube shows that the neural canal is even smaller compared to the thickness of the wall. Also the grey matter has split into the alar plate (dorsal) and basal plate (ventral).

Question 22

What do the neural crest cells form?

Answer 22

sensory neurons in dorsal root ganglia

Question 23

What occurs in the alar plate?

Answer 23

interneurons becoming specialised to receive sensory information

Question 24

What occurs in the basal plate?

Answer 24

• In the basal plate you get some interneurones and the development of motor neurones
• This means the basal plate has a motor function - the axons leave the spinal cord to go towards muscles

Question 25

In the mature spinal cord what has become what?

Answer 25

- The neural canal has become the central canal carrying CSF - Alar plates develop into the dorsal horns - Basal plates develop into ventral horns - The whole spinal cord is surrounded by a thick layer of white matter

Question 26

Describe the development of the brainstem

Answer 26

- The brainstem is a tubular structure but in the middle of it you have a 4th ventricle - The roof plate starts proliferating rapidly and the dorsal part of the brainstem expands laterally - As the roof plate expands it pushes the alar plates aside so they are no longer dorsal to the roof plate but they are actually lateral to the roof plate

Question 27

Where do the cranial nerve nuclei with motor function, sensory and autonomic function lie?

Answer 27

``` Motor = Medial Sensory = Lateral Autonomic = in between ```

Question 28

Which part of the neural tube develops in to the brain and what are the three primary vesicles formed? (4 weeks)

Answer 28

Only the most anterior part: 1. Prosencephalon - future forebrain 2. Mesencephalon - future midbrain 3. Rhombencephalon - future hindbrain

Question 29

What happens to the neural tube that doesn't form the brain?

Answer 29

Becomes the spinal cord

Question 30

What happens at the fifth week in brain development?

Answer 30

- The most anterior vesicle divides in two and the third vesicle also divides in two - This produces 5 secondary vesicles - There is an expansion of the top part of the developing forebrain - This telencephalon will become the cerebral hemispheres - There is less expansion in the lower part of the developing forebrain because that part becomes the diencephalon - The developing midbrain doesn't expand very much - The developing hindbrain divides in two to becomes the pons and the medulla

Question 31

What happens during week 8 in terms of brain development?

Answer 31

- As development continues you get more growth of the wall of the neural tube - The space within it has become smaller relative to the wall and this space becomes the ventricular system - Coming quite late, you have the first development of the cerebellum - out-pouching from the back of the pons - The telencephalon has got so big that it's starting to move back and cover the diencephalon

Question 32

How does the folding of the brain occur?

Answer 32

The vesicles aren't in a straight line - there are 3 flexures - The flexures are named based on their position - As you go through development these flexures become exaggerated

Question 33

What are the 3 flexures?

Answer 33

from tip to middle: | cephalic, pontine, cervical

Question 34

What is the structure of the brain in terms of matter?

Answer 34

grey outside and white inside

Question 35

Describe the development of the cortex

Answer 35

- The neuroblasts are proliferating near the inner membrane. - Some of the neuroblasts will stay in the middle and form the basal ganglia - There are other neurones that then migrate towards the outer membrane. - This migration takes place by the neuroblasts attaching themselves to radial glial cells - these have their cell bodies anchored in the inner membrane and have a single long process that goes to the outer membrane. - They climb up towards the outer membrane - You get a wave of proliferation near the inner membrane and then a wave of migration towards the other surface and then one layer of the cortex is formed. - Then you get another wave of proliferation and another wave of migration forming the 2nd layer of cortex - This continues until you have six layers of cells within the cerebral cortex - Each layer of cells has different types of cells with different functions and different connections - There will be problems later on if something disrupts the production of these layers

Question 36

What does normal nervous system development depend on?

Answer 36

Depends on the coordinated completion of several complex processes E.g. proliferation, differentiation, migration, axon growth and synapse formation

Question 37

What can cause developmental abnormalities?

Answer 37

• Genetic mutation and environmental factors such (mother’s lifestyle, diet and teratogens) can interfere e.g. B12 (low)

Question 38

When do developmental abnormalities occur in gestation?

Answer 38

early in pregnancy

Question 39

What causes Sz?

Answer 39

A malfunction of neural development

Question 40

What does a deficiency in folic acid lead to?

Answer 40

spina bifida

Question 41

Give examples of developmental disordes

Answer 41

- craniorachischisis (completely open brain and spinal cord) - anencephaly (open brain and lack of skull vault and brain matter) - encephalocele (herniation of meninges and brain due to skull not forming properly) - Iniencephaly (occipital skill and spine defects with extreme retroflexion of head) - spina bifida occulta (some of vertebrae not completely closed) - closed spinal dysaphism (deficiency of atleast two vertebral arches) - meningocele (pertrusion of meninges through defect in skull or spine) - myelomeningocele (open spinal cord as well as meningeal cyst)