Congenital disorders associated with CNS

Question 1

Closures in humans and mouse

Answer 1

In mouse, closure 1 is located at the edge between the hindbrain and spinal cord
Closure 2 is located between the forebrain and midbrain
Closure 3 is located in the most rostral portion of the forebrain
In human we have the same 3 closure points plus 2 additional ones an these are:
Closure 4 which occurs more rostrally with in the hindbrain
than closure 1
And closure 5 which is located at the very posterior portion of the neural plate
Closures are a part of the primary neurulation mechanism

Question 2

the 2 modes of neural tube closure

Answer 2

-Primary neurulation: 
• rolling-up of tube 
• closure is by fold apposition then "zipping-up" 
• Finally, at cranial and caudal neuropores
-Secondary neurulation: 
• tunnelling or hollowing of tail bud 
-The primary and secondary neural tube 
become continuous 
• Somites 30-31 in human (2nd sacral)

Question 3

how does the shaping of the neural plate occur

Answer 3

by convergence/ extension

Question 4

Primary neurulation: cellular and

molecular mechanisms

Answer 4

• Shaping of the neural plate occurs by
convergence/extension
• Tubing requires bending at hinge points
• Cell wedging at hinge points: microtubules & actin
filaments
-Controlled by the Planar Cell Polarity pathway

Question 5

The Wnt-PCP pathway

Answer 5

-Wnts: secreted signalling molecu les — the ligand
-Frizzleds: Wnt receptor,
transmembra ne proteins
-Vangl and Celsr: co-receptors
necessary for signal transduction
-Dv11-3: cytoplasmic proteins, activated
upon interaction between Wnts and
Fzds

Question 6

what is Chraniorachischisis

Answer 6

when the neural plate is abnormally
broad with a non-bending
region between neural folds

Question 7

Neural Tube Defects in humans

Answer 7

Anencephaly: cranial neuropore failure 
— perinatal lethal (also craniorachischisis) 
Spina Bifida: caudal neuropore failure 
— Occulta (unfused vertebral arches) 
— Meningocoele 
—Meningomyelocoele 
—Myeloschisis aperta

Question 8

Environmental factors associated to NTDs

Answer 8

Maternal diet 
• Vitamin deficiency/malnutrition 
---Folate 
---Inositol 
• High levels of sugar 
Maternal obesity 
Diabetes 
Hypertermia Teratogenic agents 
• Valproic acid (VPA)

Question 9

Relationship between folic acid and NTD

Answer 9

inversely proportional