Congenital Diseases Associated With The Central Nervous System Flashcards
What does the neural tube give rise to?
Brain Spinal cord Cranial and spinal nerves Eyes and other sensory organs Neural crest
When is the neural tube formed?
In gastrulation at week 3/4
What happens as the neural tube closes?
Becomes patterned along the dorso-ventral and rostro-caudal axis
What are defects classified according to?
Stage thought to be affected
What are the classifications of neural tube defects?
Early CNS patterning
Neural tube closure
Regional brain defects
What is an example of an early CNS patterning defect?
Holoprosencephaly
What are some examples of neural tube closure defects?
Chraniorachischsis
Exencephaly
Spina bifida
How many neural tube closure points are there?
Three main and two others
Where is the first closure of the neural tube?
Between hindbrain and spinal cord
Where is the second closure of the neural tube?
Between forebrain and midbrain
Where is the third closure of the neural tube?
Most rostral portion of forebrain and only progresses posteriorly
Where is the fourth closure of the neural tube?
More rostral and within the hindbrain than closure 1
Where is the fifth closure of the neural tube?
Most posterior point so only progresses anteriorly
What are the two modes of neural tube closure?
Primary or secondary neurulation
What happens in primary neurulation?
Rolling up of tube
Closure is by fold apposition then ‘zipping up’
What is secondary neurulation?
Tunneling or hollowing of tail bud
What are the steps in primary neurulation?
Shaping Folding Elevation Convergence Closure
What happens in the shaping step of primary neurulation?
Narrowing along the mediolateral axis and extend along the rostro-caudal axis
What happens in the folding step of primary neurulation?
Occurs by the establishment of hinge points along the neural plate
What is the first hinge point to appear in primary neurulation?
Midline hingepoint
What happens in the elevation step of primary neurulation?
Lateral wings of neural plate to fold up
What happens in the convergence step of primary neurulation?
More hinge points formed next to the neural crest which allows for the rounding of the plate
What causes the cell wedging at hinge points in primary neurulation?
Microtubules and actin filaments
What is primary neurulation controlled by?
Planar cell polarity pathway
What is convergence-extension?
Process of lengthening by narrowing
What does convergence-extension require?
Cells to become polarised in the plane of the cell layer
What is convergence- extension controlled by?
Wnt-PCP pathway
What are the names of coreceptors necessary for signal transduction?
Vangl and celsr
What does the wnt-PCP pathway lead to?
Regulation of transcription and regulation of the cytoskeleton
What do mouse mutants in components of the wnt-PCP pathway show?
Neural tube defects:
Abnormally broad neural plate with a non-bending region
What is cell wedging?
Mechanism by which the hinges on the neural plate are formed
What is cell wedging caused by?
Cytoskeleton remodelling at the apical cortex
What maintains the shape of subapical epithelial cells?
Lots of actin filaments that maintain the shape of cells
What are some environmental factors that are associated with neural tube defects?
Maternal diet/obesity
Diabetes
Hypertermia
Teratogenic agents
What is hypertermia?
Severe disease that includes high temperature in early pregnancy
What is an example of a teratogenic agent?
Valproic acid
How much folic acid does a pregnant women with no NTD history need to take?
0.4mg/day
How much folic acid does a pregnant women with a NTD history need to take?
5mg/day
