congenital disease associated with CNS

Question 1

describe the 2 modes of neural tube closure

Answer 1

1 = rolling up of tube
closure by fold apposition then zipping up at cranial and craudal neuropores

2 = tunnelling/hollowing of tail bud

1 and 2 neural tube becomes continuous
- located at somites, 30-31 in human

Question 2

steps of primary neurulation

Answer 2

1. shaping of neural plate occurs. neural plate narrows down along lateral axis and extends
2. folding then occurs. hinge points allow folding. median hinge point (along midline)
3. wings form along median hinge point = elevation
4. convergence = edges further apart = more hinge points. folds fuse with each other
5. closure = complete closure of neural plate occurs

• shaping of neural plate occurs by convergence
• tubing requires bending at hinge points
• cell wedging at hinge points = microtubules and actin filaments
  = both controlled by: planar cell polarity pathway

Question 3

describe convergence

Answer 3

lengthening by narrowing of a tissue, requires all cells to become polarised

Question 4

what is the planar cell polarity pathway

Answer 4

mouse mutants in components of pathway show neural tube defects
celsr1-1-
vangi-1-
scribble-1-

Question 5

environmental factors associated to NTDs

Answer 5

maternal diet = vitamin deficiency/malnutrition 
high levels of sugar 
maternal obesity
diabetes
hyperthermia 
teratogenic agents e.g valproic acid

Question 6

describe folic acid and NTDs

Answer 6

more folic acid = decreased recurrence risk
5mg recommended to women who’ve experienced previous problems
folic acid is the only known intervention preventative for any congenital anatomy
no adverse effects: maybe B12 deficiency, mask anaemia, promotion of colon polyps cancer = DILEMMA
reduce palate and heart defects
up to 70% of NTP can be prevented by folate

INOSITOC = can prevent NTDs in experimental models