Neural Tube

Question 1

WHat are the two defects from neural tube defects?

Answer 1

Spina bifida and Anacephaly

Question 2

Describe Spina bifida (SB) features:

Answer 2

-Sac of CSF accmulates under spinal cord
-Not fatal
-Folic acid supplement prevents SB >70%
-Requires fetal or postnatal surgery to prevent nerve damage/infection
-Neurons should have differentiated causes automatic dysfunction, lose skin sensation, lck of motor movements causing bladder control

Question 3

Describe Anacephaly (Ana) features:

Answer 3

-Fatal
-Female embroys affected 2x more
-Better folic acid supplmentation than SB
When anterior neuropore does not close

Question 4

What causes SB?

Answer 4

Incomplete closure of posterior neuropore
Exposed regions of the neuroepithelium as it doesn’t get covered by skin or surface ectoderm.

Question 5

What causes Ana?

Answer 5

When the brain doesn’t fully close during early development- the brain develops outside the head (this part is anencephaly) and when the brain collapses back into head is called anencephaly.

Question 6

What can cause neural tube defects

Answer 6

Genetic inheritence- folate metabolism genes mutation

Enviroment- obesity, high temperature

Nutrition: folic acid Vit B6 defiency
uncontrolled diabetes

Question 7

Other types of NTD?

Answer 7

Zika virus causing microcephaly

Question 8

What are the open regions of neural tube called

Answer 8

Neuropore

Question 9

Describe primary neurulation

Answer 9

Primary neurulation involves the neural plate folding inward and fusing to create the neural tube

Question 10

Describe secondary neurulation

Answer 10

secondary neurulation involves the formation of the neural tube from a solid cord of cells that cavitates (hollows out)

Question 11

What 3 cell types make up neural tube

Answer 11

1.Mesoderm
2.Surface ectoderm
3.Neuroepithelium

Question 12

Define zippering point

Answer 12

Point where the neural tube folds to begin neural tube closure.
Distruption to zippering causes NTD

Question 13

What does mesoderm create?

Answer 13

Epidermis, carlidge and bone

Question 14

What does surface ectoderm create?

Answer 14

Future skin cells

Question 15

What do neuroepithelial cells create?

Answer 15

give rise to nerual cells types, neurons first then glial at later stages.

Question 16

What is the order of closure points in CNS?

Answer 16

Closure 1- hindbrain/cervial
Closure 3- forebrain
Closure 2-Midbrain/Forebrain
Closure 5 (Galea et al,2017)

Question 17

Which closure points do humans not have but mice do?

Answer 17

Closure 2

Question 18

What the three neuropore sites?

Answer 18

Hindbrain (HNP)
Anterior (ANP)
Positeror (PNP)

Question 19

How long it takes to close in humans verus mice

Answer 19

mice ~2 days
humans ~5 days

Question 20

What are the steps for closing neuropore?

Answer 20

1. Elevation
2. Hinge points (neural folds bend)
3. Zippering (neural fold fuses)

Question 21

What is the process of neuralation?

Answer 21

Where the neural fold evelates, fuses and closes the neural tube

Question 22

What is mode 1 hinge point

Answer 22

Near cervial spine
Medial hinge point so V shaped

Question 23

What is mode 2 hinge point

Answer 23

Thoracic
medial and dorsolateral hinge points

Question 24

What is mode 3 hinge point

Answer 24

Lumbar
Dorsolateral widens and lose medial hinge points

Question 25

Which modes of closure do mice have?

Answer 25

Mice do not go from mode 1 to mode 2 stop closing the spinal cord at thoracic level.

Question 26

What techological advance did they have in imaging?

Answer 26

Up until this point, they were only able to look at fixed cross sections of embryos. Now they moved onto live imaging under confocal microscope, One of the disadvantages of confocal imaging for live embryos is phototoxicity from the lasers. They used two photon excitations to mitigate against that.

Question 27

How does zippering occur on cellular level

Answer 27

Narrowing before shortening of neuroepithelial cells apically constrict. Neural epithelium narrows and shrinks apically by recruiting actomyosin- causes muscle constriction. Cells are attached dto one another so actomyosin constriction causes bending of the whole tissue.

Question 28

How neural tube closes - 6 steps

Answer 28

1.Dorsal bending of the flat neural plate 2.closure 1 formation 3.zippering down the spinal cord and up the hindbrain 4.closure 3 then closure 2 formation 5.ANP then HNP closure 6.PNP closes

Question 29

What is the role of neruoepithelium in NT closure

Answer 29

Apical constrcition Not fusion or zippering

Question 30

Limitation of pharma block of ROCK

Answer 30

1.Inhibiting ROCK- expressed elsewhere 2.Intervariability 3.Off target effects even if highly selective

Question 31

Advantages of ROCK pharma block

Answer 31

1.Reversible 2.Temporal timing

Question 32

How does the surface ectoderm influence in NT closure? x2

Answer 32

Influences length of neuropore Influences width of neuropore

Question 33

Width change of surface ectoderm

Answer 33

Promoted neruoepithelium bending Anti-closure tension

Question 34

Length change of surface ectoderm

Answer 34

Actomyosin cable constriction Zippering

Question 35

What was the curly tail mouse model and whatb did it show about SB & Ana ?

Answer 35

first models studying neural tube formation/closing bred mice with curly tails - saw these mice had spina bifida & Ana- they are related conditions

Question 36

How did curly tail models help with diagnosis

Answer 36

Found alpha fetal protein in NTD was higher in embryons with Ana and SB - picked up through amnicentesis

Question 37

What did curly tail models reveal about mechanism of NTD (1992)

Answer 37

failure to shorten and narrow the PNP. Discovered in curly tail mice- SEMINAL STUDY An abnormally wide PNP Also showed folic acid would help with this.

Question 38

What things may help SB and Ana

Answer 38

Inositiol- Vit B8