How to make a brain - development of CNS

Question 1

What does the CNS develop from?

Answer 1

The CNS develops from a tiny patch of neural plate (ectoderm)

Question 2

What factor regulates growth within development to stop us from being all nervous system?

Answer 2

We would be all nervous system if it wasn’t for BNP which makes skin etc, BNP is inhibited during nervous system growth

Question 3

Mention how early development occurs and what it looks like up to day 19?

Answer 3

In early development we have a neural plate which has columnar epithelium (neurectoderm) on its surface and sits above the notochord.

The plate will make a tube which is called neurulation and around day 19+ a midline groove becomes apparent. Neurulation is induced by the bar shaped tissue - notochord (deep to neural epithelium)

Question 4

How does development look around days 20-21 (third week)?

Answer 4

On days 20-21 the cells on the plate edge thickens forming folds and a groove referred to as the neural fold and groove (looks like a trench dug out in middle). Somites start to form in the midline of the edges of the tube.

Question 5

What happens around the fourth week?

Answer 5

Contractile actin at apex of each cell, constricts and makes apex smaller, bases stay same and get curvature

Cells on edges of folds start to sense each other and throw out projections so they touch and adhere and this starts to form the neural tube

The starts initially in the cervical region

This process is called neruilation ( ormation of tube from plate)

Question 6

What occurs around day 25 and day 27?

Answer 6

Closure of the neural tube occurs at the rostral end at day 25 and you have a rostral neuropore formed

And the caudal end of the tube closes on day 27 creating the caudal neuropore

Question 7

What happens if the neuropores fail to close?

Answer 7

Anencephaly (a type of neural tube defect - NTD)

Failure of neural tube to close - rostral neuropore. Causes;
- Infants to be born without a forebrain
- Usually unreactive to light and sound
- Usually stillborn
- Some infants may exhibit aspiration and respond to touch and sound if brainstem is intact.

0.5 - 1 peer 1000 live births

Question 8

What are the risk factors for developing a neural tube deficiency and what do we do to prevent it?

Answer 8

Risk factors for neural tube deficiency;
- folate deficiency
- Previous anencephaly
- diabetes
- epilepsy drugs

Its now a policy in UK if thinking of becoming pregnant supplement diet with folate

Question 9

What are the different types of defects in caudal neuropore?

Answer 9

These are all types of Spina bifida - clinically significant in 1/1000 births

• Spina bifida occulta - normal apart from hair on surface
• Meningocele - bulges but spinal cord is in spinal column
• Meningomyelocele - spinal cord protrudes
• Myeloschisis - most severe! neural tissue on arch of back
• Myeloschisis - when neuropore doesn’t close and we have folded neural tissue outside

Question 10

What is a disease marker that is used to check from neural tube defects?

Answer 10

Alpha fetoprotein (AFP)
- its also used for some cancers and liver diseases as well

Question 11

How does the neural tube form the brain?

Answer 11

3 swellings develop got become the brain;
- Prosensecephalon (becoming forebrain)
- Mesencephalon (becoming midbrain)
- Rhombencephalon (Hindbrain)

These vesicles keep connected throughout life and spinal cord is attached. This space has CSF and is continuous

Question 12

How does the forebrain, midbrain and hindbrain develop?

Answer 12

Forebrain;
- Grows two lateral expansions connected to a central slit like space

Mid brain;
- Grows slower than forebrain and remains as a single central tube

Hindbrain;
- Develops into (rest of the) brain stem and cerebellum with a central ventricle expanding

Question 13

How does the lumen of the tubes develop ?

Answer 13

Forebrain;
- Forms two lateral ventricles and a third ventricle (with thalamus around it)

Midbrain;
- Forms a cerebral aqueduct

Hindbrain;
- Forms fourth ventricle

Question 14

How do the walls of the tube develop in the forebrain?

Answer 14

The telencephalon (end brain) containing the cerebral hemispheres

Diencephalon grows containing the thalamus and hypothalamus

Question 15

How do the walls of the tube develop in the hindbrain?

Answer 15

The Midbrain (mesencephalon)

Hindbrain (Rhombencephalon) grows 2 parts;

the metencephalon containing Pons and cerebellum

the myelencephalon containing the medulla

Question 16

Why do the cerebral hemispheres grow in a curve and how does this explain the shape of the internal structures?

Answer 16

The forebrain vesicle becomes the cerebral hemispheres.

At week 6 the cephalic flexure starts to grow.

Around 12 weeks there is strong relative growth of the temporal lobes and they have outgrown their space so grows a bit like a boxers glove, growing downwards and forwards making a C-shape. This also grows around the developing insulation hence why it becomes an island surrounded by temporal, parietal and frontal lobes.

If you remember C shape of lateral ventricles this will help

Question 17

What happens around 16 weeks to the shapes of our cerebral hemisphere?

Answer 17

The cerebral hemisphere is c-shaped, can see central sulcus and lateral fissure with insula buried.

The brain has a more crinkled surface which is more gyro to increase surface and volume of grey matter

Question 18

How does the curved growth affect the shape of the internal structures of the brain?

Answer 18

The following structures are curved;

The corps callosum - a huge hemisphere connection

The fornix (important for memory (connects hippocampus with anterior structures) - growth of temporal lobes creates looping in fornix

Hippocampus (memory function) due to fornix getting longer thee hippocampus descends into the temporal lobe

Lateral ventricle

Interventricular foramen - fluid filled space

Question 19

How can we see these c-shapes in the adult brain?

Answer 19

Can see c-shaped corpus callosumn, how 3rd ventricle loops, the fornix

Question 20

What forms our c-shaped internal grey matter?

Answer 20

Basal ganglia - contains caudal nucleus which follows shape of lateral ventricle

Question 21

How is Basal ganglia split?

Answer 21

Its split by ascending and descending white matter bundle - the internal capsule

It splits apart the caudate nucleus and the lentiform nucleus (which contains putamen + globus pallid us)

Question 22

What components form the basal ganglia and draw how they are arranged?

Answer 22

Putamen is part of the lentiforrm nucleus which also includes globes pallidus hidden within it. It looks like a big stone in the middle.

The caudate nucleus attaches to this and wraps itself around the putamen in a c-shape.

The internal capsule is located around the middle at the superior end of the caudate nucleus and the thalamus is located more medial-inferiorly to the putamen.

The amygdala is NOT a basal ganglia structure but is at the end pf the caudate nucleus.

There is also substantial nigra and sub thalamus that are part of basal ganglia but elsewhere

Question 23

How does the fourth ventricle form?

Answer 23

Around week 6 the poutine flexure appears and widening of the roof of the fourth ventricle occurs.

Question 24

What happens to the sensory grey matter before and after the back of the brain stem is opened out?

Answer 24

Sensory grey matter is in dorsal position before the 4th ventricle forms

After the 4th ventricle forms the sensory grey matter tends to be more lateral

Question 25

How does the cerebellum develop?

Answer 25

The cerebellum develops in the dorsal wall of the neural tube.

Question 26

How does the brain stem look once development has occurred?

Answer 26

Grey matter in brain stem is dorsal rather than ventral

There is a superior and inferior colliculus in the midbrain

The floor of the 4th ventricle is in the pons

There is fasiculus cuneatus and fasiculus gracillis in the medulla

Question 27

What side do the 12 cranial nerves exit ?

Answer 27

They exit ventrally as the grey matte is at the back of the brainstem so cranial nerves come out front

Question 28

What does the caudal neural tube develop into?

Answer 28

The caudal neural tube becomes the spinal cord.

The caudal neural tube has three layers which will undergo cell division to make;

• Ventricle layer - which will make progenitor cells, neurons/glia for the mantle layer
• Mantle layer - will make neuron bodies/glia
• Marginal layered processes of neuron build here (white matter conc on outside)

Question 29

What are regions called as the spinal cord develops?

Answer 29

Sulcus limitans - sulcus in middle

Alar lamina (posterior basal lamina) - becomes sensory (somatic/visceral)

basal lamina (anterior basal lamina) - becomes - motor somatic/visceral

Question 30

How does the connections to the PNS grow?

Answer 30

Ingrowth of neurites from the dorsal root ganglion cells (DRG) forms dorsal root

Outward growth from neurons motor grey forms ventral root

Question 31

What induces the neural tube formation and nerve cell specialisation?

Answer 31

We would be all nervous system if it wasn’t for BNP - Bone morphogenetic protein which inhibits neural ectoderm, promoting skin

Noggin, chordin, follistatin produced in the notochord block BMP - allows default differentiation of neural ectoderm

Question 32

What happens neural test cells ?

Answer 32

Neural crest undergo a transition and instead of being stuck there they then become migratory and spread through embryo giving arise to a wide range of tissues

Question 33

Neural crest cells give rise to so Manny cells but what are the main ones in the CNS that they give rise to and why is it important we know these?

Answer 33

• Cranial nerve ganglia
• Autonomic ganglia
• Schwann cells
• Craniofacial skeleton
• Melanocytes

This is important as a defect in neural crest cell can be fatal to a developing embryo as they make so many key things

Question 34

Name 2 neural crest development disorders ?

Answer 34

Waardnburg’s syndrome (autosomal dominant 1/50,000)
- Some types have Pax-3 gene deletion which controls some aspects of neural crest
- Pigment abnormalities (even albinism) (1 lock of hair white like cruel de vill)
- Deafness
- Constipation
- Heterochomia of eyes
- Telecanthus - widen spaces of eyes

Treacher Collins Syndrome (autosomal dominant 1/50,000)
- Defective protein called Treacle (TCOF1 gene)
- Failure of formation/apoptosis of neural crest cells
- Abnormal eye shape
- Micrognathia
- Conductive hearing loss
- Underdeveloped zygoma
- Malformed ears
- Craniofacial skeleton developed incorrectly