L2: Neural Tube Deficits Flashcards
what causes perinatal death
stillbirth and neonatal deaths
what is the biggest cause of stillbirths
anencephaly
CNS malformation stats
1 per 1000 pregnancies
over 250000 cases per year
main types of NTDs
anencephaly (40%)
open spina bifida (40%)
craniorachischisis (<10%)
encephalocele (10%)
what are the 2 phases of neuralation
primary and secondary
what is primary neuralation
neural tube folding and closure (in the midline by the notochord)
what is secondary neuralation
canalisation (no closure in the lower body)
days of neural tube closing in mice and humans
8-10 days in mice
21-28 days post fertilisation in humans
how many neural tube closures
1,2,3
humans do not have closure 2
what does the failure of closure 1 lead to
craniorachischisis
what does failure of closure 3 lead to
anencephaly (failure of anterior neuropore to close)
what does the failure of the posterior neuropore closing lead to
closed spinal dysraphism and open spina bifida (myelomeningocele)
how is walking affected if lesion is above/below the lumbar and sacral
if lesion is above - no walking
if lesion is below - walking
what are the two hits in development of open NTDs
1)failed cranial neuralation - neural tube does not close
2) exencephaly - tissue is viable and undergoes apoptosis
how to stop 2nd hit in spina bifida
in utero surgery to cover lesion (stops infection in the foetus)
genes involved in the failure of neural tube closure
Vangl2, Scrb1, CelSr1
planar cell polarity signalling pathway
wnt5a&11 (external) bind to frizzled receptors causing change in conformation, forms complex
role of PCP
regulate cytoskeleton (actin and myosin)
regulates cell shape and movement
what does the disturbance of PCP cause
misexpression of Dishevelled/strabismus leads to open neural tube phenotype and short and broad body axis (No convergent extension)
what mutant leads to no convergent extension
Vangl2 lp/lp (mouse)
what does the vangl2lp/lp mutant cause
disrupted midline bending
no convergent extension
too many cells in midline
mechanical issue
no cell fusion
established causes of NTDs
valproic acid (spina bifida taken for epilepsy)
fumonisin (fungal toxin from maize crop)
NTD associations
diabetes
obesity
hyperthermia
fever
retinoids
alcohol
what deficiencies cause NTDs
folate
vitb12
inositol
zinc
