1. Development of CNS

Question 1

Describe the structure of the embryonic disc at 3 weeks (transverse section)

Answer 1

• 3 layers (inside => out)
- endoderm
- mesoderm
- ectoderm
• Neural plate - proliferation of ectoderm in dorsal midline
• Notochord - cartilaginous strip running through embryo (between endoderm and neural plate), in middle of mesoderm), ultimately forms the vertebral column

Question 2

Describe the development of the embryonic disc

Answer 2

• As the neural plate thickens, it starts to fold up on the sides
• The 2 neural folds fuse dorsally (away from endoderm) to form a tube - neural canal
• Bunch of cells at tip of neural fold - neural crests
• Neural tube and neural crest are 2 independent sources of nervous tissue
- neural tube: all CNS cells
- neural crest: all PNS cells
• Neuroepithelium - wall of neural tube

Question 3

Describe the 3 types of cells of the neuroepithelium

Answer 3

• Neuroblasts - all neurones with cell bodies in the CNS (include motor neurones)
• Glioblasts - become neuroglia (astrocytes and oligodendrocytes)
• Ependymal cells - line the ventricles and central canal (remain close to the inner membrane of the neural tube and spread out and form a lining around the developing ventricular system)

Question 4

Where do microglia originate?

Answer 4

• Peripheral origin

* From systemic system => populate brain in early development

Question 5

What are the 4 types of neural crest cells?

Answer 5

• Sensory neurones of dorsal root ganglia and cranial ganglia
• Postganglionic autonomic neurones
• Schwann cells
• Non-neuronal derivatives e.g. melanocytes

Question 6

What is a common feature of neural crest derived cells?

Answer 6

Capable of migrating over quite large distances

Question 7

Briefly describe the cross-section of the wall of the neural tube at an early stage

Answer 7

• Almost all cells attached to inner and outer membranes
• Nuclei of each cell in different positions
• Bigger cells near the inner membrane undergoing mitosis

Question 8

Describe the differentiation of the neuroepithelium

Answer 8

• Cells withdrawing from the outer membrane => inner membrane (=> mitosis)
• One of the daughter cells stay attached to the inner cell membrane - gets bigger and goes into cell cycle again
• Other daughter cell migrates away and develops into neuroblasts
- develop processes (one becomes axon)
- axons are directed away from the inner membrane
• End up with 3 layers
- ependymal layer - by inner membrane (where mitosis occurs)
- grey matter - mainly cells bodies
- white matter - mainly axons

Question 9

How is the differentiation of glioblasts and different to neuroblasts?

Answer 9

• Glioblasts can migrate into white matter as well

* Glioblasts do not develop axons (but do develop processes)

Question 10

Describe the layers of the neural tube in cross-section

Answer 10

• Neural canal in centre
• Ependymal layer surrounds neural canal
• Roof plate (most dorsal part of canal)
• Floor plate (most ventral part of canal)
• Grey matter = mantle layer
• White matter = marginal layer
• Neural crests further out

Question 11

What molecules control the whole process of differentiation and migration in the neural tube, and how?

Answer 11

• Signalling molecules, secreted from tissues around or cells within the neural tube
• Interact with receptors on the developing neuroblasts
• Guide the developing axons
• Can cause attraction or repulsion - direction determined by concentration gradient (higher conc. closer to signalling molecules)
• Timing is important - some signalling molecules have different effects at different stages of development, neurones need to have the right receptors

Question 12

How does the neural canal and grey matter change at a later stage of development?

Answer 12

• Neural canal is even smaller compared to the thickness of the wall
• Grey matter splits into 2 different types:
- Alar plate - dorsal - sensory
- Basal plate - ventral - motor

Question 13

What information do the interneurons in the alar plate receive?

Answer 13

• Sensory information

* From developing dorsal root ganglia (developed from neural crest)

Question 14

Where does information from the basal plate go?

Answer 14

• Motor function
• Interneurons and developing motor neurones
• Therefore, axons leave spinal cord here, to go towards muscles

Question 15

How is the white matter of the spinal cord split in later development?

Answer 15

• It isn’t dorsal/ventral

* It is mixed

Question 16

Describe the cross-section of a mature spinal cord

Answer 16

• (neural canal is now) Central canal carrying CSF
• (Alar plate is now) Dorsal horns
• (Basal plate is now) Ventral horns
• Dorsal root joins dorsal root ganglion
• Ventral root joins further down
• Whole spinal cord (horns and canal) is surrounded by thick layer of white matter

Question 17

Describe the gradient of molecules around the notochord and how this effects cells in the neural tube

Answer 17

• Several signalling molecules produced by notochord
• Concentration gradient established
• Highest concentration near notochord
• Cells closest to molecules induced to become motor neurones
(• Molecules produced by ectoderm, dorsally, inhibit differentiation into motor neurones)

Question 18

Describe the development of the brainstem

Answer 18

• Firstly, development of 4th ventricle
• Roof plate (dorsal/posterior) starts proliferating rapidly and dorsal part of brainstem exapnds laterally
• Roof plate pushes alar plates aside from dorsal to lateral to the roof plate
• Cranial nerve nuclei with motor function tend to lie more medially - where the basal plates are
• Sensory - lateral
• Autonomic - in between

Question 19

What are the three primary vesicles that the wall of the anterior neural tube differentiates into - at around 4 weeks (which will develop into the brain)?

Answer 19

• Prosencephalon - future forebrain
• Mesencephalon - future midbrain
• Rhombencephalon - future hindbrain

Question 20

Following the 4th week, how do the vesicles divide in the formation of the brain?

Answer 20

• Prosencephalon (most anterior) => telencephalon + diencephalon
• Mesencephalon doesn’t divide
• Rhombencephalon => pons + medulla
• Therefore, 5 secondary vesicles present at 5 weeks

Question 21

What happens to the developing forebrain following the 5th week?

Answer 21

• Expansion of telencephalon (top/anterior part)
• Develops into cerebral hemispheres (cerebral cortex)
• Less expansion in lower part
• Diencephalon - thalamus and hypothalamus

Question 22

What happens in the developing brain around 8 weeks?

Answer 22

• Growth of wall of neural tube
• Space within becomes smaller => ventricular system
• 3rd ventricle forms in diencephalon (forebrain)
• Aqueduct becomes narrow (midbrain) - drains into 4th ventricle (hindbrain)
• First development of cerebellum - from the back of the pons

Question 23

When looking at a lateral view of the developing brain at 4 weeks, what are the flexures called, starting anteriorly?

Answer 23

• Cephalic flexure
• Pontine flexure
• Cervical flexure

Question 24

Describe the proliferation and migration of neuroblasts in the wall of the developing hemisphere of the brain

Answer 24

• Proliferate near inner membrane
• Some stay in the middle to form the basal ganglia
• Others migrate towards the outer membrane
- attach to radial glial cells (like scaffolding)
- cell bodies anchored in inner membrane and have a single long process to the outer membrane
• Wave of proliferation near inner membrane then wave of migration to outer surface forming one layer of cortex
• Waves continue until you have six layers within cerebral cortex
• 1st layer - acellular, local connectivity layer to neurones below
• Layers 2-6 - lamina of neurones, functional connections in fully developed brain
• Each layer has different types of cells with different functions/connections

Question 25

In which trimester/weeks of pregnancy does the majority of brain development take place?

Answer 25

1st trimester - first 12 weeks

Question 26

What can disrupt brain development during pregnancy

Answer 26

• Genetic and environmental abnormalities:

• mother’s lifestyle
• diet (folate and vit B12)
• teratogens (agent that disrupts development of embryo)

Question 27

What neural tube deficit can a deficiency of folic acid lead to?

Answer 27

Spina bifida

Question 28

What does rostral and caudal mean?

Answer 28

• Rostral - towards head

* Causal - towards spinal cord

Question 29

Give 2 examples of rostral neural tube deficits

Answer 29

• Anencephaly - lack of brain

* Encephalocele - herniation of brain through the unfused skull (ectopic brain substance - out of skull)

Question 30

Give 4 examples of causal neural tube deficits

Answer 30

• Spina bifida - lack of closure of chordal part of tube (may not be visible externally)
• Dysraphism - lipoma formed, large fatty deposit
• Meningocele - meninges herniate
• Myelomeningocele - spinal cord herniates