L18: Congenital Diseases Associated With CNS

Question 1

What are the closures of the cranial and caudal neuropores?

Answer 1

→closure 1,2,3,4 and 5

Question 2

What are the two modes of neural tube closure?

Answer 2

→primary neurulation

→secondary neurulation

Question 3

What is primary neurulation?

Answer 3

→rolling-up of tube

→closure is by fold apposition then “zipping-up”

Question 4

Where does secondary neurulation occur?

Answer 4

→occurs at most caudal region of neural tube

Question 5

Where do the primary and secondary neural tube become continuous?

Answer 5

→Somites 30-31 in human (2nd sacral)

Question 6

What happens during primary neurulation?

Answer 6

→Shaping of the neural plate occurs by convergence/extension

→Tubing requires bending at hinge points

→Cell wedging at hinge points: microtubules & actin filaments

Question 7

What is primary neurulation controlled by?

Answer 7

→Planar Cell Polarity pathway

Question 8

What does the lengthening process require?

Answer 8

→cells to become polarised

Question 9

What axis does tissue elongation occur?

Answer 9

→octagonal axis

Question 10

What are Vangl and Celsr?

Answer 10

→co-receptors necessary for signal transduction

Question 11

What is Dvl-1-3?

Answer 11

→cytoplasmic proteins, activated upon interaction between Wnts and Fzds
→first to be activated

Question 12

Which pathways can be mutated to show neural tube defects?

Answer 12

→celsr1-/- (crash)
→vangl-/- (loop-tail)
→scribble-/- (circletail)
→dvl1/2
→fzd3/6

Question 13

What associations are to do with PCP genes?

Answer 13

→craniorachischisis

Question 14

What is chraniorachischis?

Answer 14

→non-bending region between neural folds

→ Defective convergence/extension and cell wedging

Question 15

What is cell wedging?

Answer 15

→individual epithelial cells by contraction of their apical ends driven by myosin motor proteins acting on actin filaments

Question 16

Which mutations show associations with craniochischisis and other NTDs?

Answer 16

→ PCP genes

Question 17

What causes cell polarity?

Answer 17

→ apical and non-apical sides

Question 18

What localises actomyosin to the apical surface?

Answer 18

→ Wnt-PCP inn a mediolateral polarised way

Question 19

Give two examples of neural tube defects in humans

Answer 19

→ ancephaly

→ spina bifida

Question 20

What is ancephaly?

Answer 20

→ cranial neuropore failure

→ perinatal lethal

Question 21

What type of failure is spina bifida?

Answer 21

→ caudal neuropore failure

Question 22

What are the 4 types of spina bifida?

Answer 22

→ Occulta (unfused vertebral arches)
→ Meningocoele
→ Meningomyelocoele
→ Myeloschisis aperta

Question 23

What are environmental factors associated with NTDs?

Answer 23

→Maternal obesity
→ Diabetes
→ Hypertermia
→ Teratogenic agents
→ maternal diet

Question 24

What is a teratogenic agent that can lead to NTD?

Answer 24

→ Valproic acid (VPA)

Question 25

How is folic acid deficiency being addressed?

Answer 25

→Supplementation dose: 0.4mg/day or 5.0 for pregnant women

→ mandatory cereal grain fortification in USA

Question 26

What are the suggested problems of folic acid supplements?

Answer 26

→ B12 deficiency (reduce detection by masking anaemia, allowing neurotoxic complications)

→ promotion of colon polyps to cancer

Question 27

Which NTDS cannot be treated with folic acids?

Answer 27

→ folate resistant NTD

Question 28

What is cell polarity controlled by?

Answer 28

→ Wnt pathway