Lecture 4: Brain Embryology Flashcards
Why is studying brain development important?
a defect in brain development can cause epilepsy, learning disability, intellectual disability, autism spectrum disorder, brain cancer
What is the oldest way of looking at the brain?
pathology
What brain imaging techniques are used when studying brain embryology?
pathology and MRI shows us what happens to the brain development
genetics is useful to understanding what causes the normal and abnormal behavior
What are the genomic methods used when studying brain embryology?
karyotype
CGH
next-generation sequencing
What are the major steps in the development of the brain?
gastrulation
primary neurulation
porencephalic development
neuronal proliferation
neuronal migration
organization
myelination
What is gastrulation?
formation of three layers of cells
endoderm (inside)
mesoderm (middle)
ectoderm (exterior, neuron, skin)
What is neurulation?
neurulation refers to formation of the neural tube from a flat layer of ectodermal cells
What are the important genes in neurulation?
TGF-beta
BMF
Sonic Hedgehog (SHH)
some genes are expressed in dorsal aspect and other in the ventral
SHH is secreted initially from the notochord
What is neural tube closure?
the neural tube needs to close at each extremity
anterior neural pore closure (at the top): 24-25 days
posterior pore closure (at the bottom): 25-28 days
top closes first than bottom
What is anencephaly?
defect of anterior neuropore closure
result in anencephaly
this type of lesion is frequently not compatible with life
What is spina bifida?
failure of closure of the posterior neuropore leads to spina bifida (with various motor defects in the leg of the child)
more likely at the bottom of the spine because it takes longer to close
What is prosencephalic development?
the anterior part of the neural tube splits into 2 prosencephalic vesicles
starts to look more like two hemispheres
What is holoprosencephaly?
failure of cleavage of the 2 hemispheres
lack of separation of the two hemisphere
What genes are associated with holoprosencephaly?
the sonic hedgehog pathway (SHH) pathway
What is the SHH pathway?
the SHH pathways involves the patched and smoothened receptors and the secondary messenger GLI that results in transcription of DNA and proliferation
What occurs around 2 weeks of gestation?
the formation of the brainstem
What is mobius syndrome?
congenital partial or complete facial diplegia
other cranial nerve palsy (6th, 3rd)
malformation of the limbs (equinovarus)
disease of brainstem development
cause: Hoxb-1 and Hoxb-4
What are homeobox (HOX) genes?
homeobox (HOX) genes are important for patterning in flies and mammals
gens are organized, not a random order
patterning is similar between species, placed with some correlation to what they do in the body
genes involved in development are similar between species
What is neuronal proliferation?
the brain is thicker than a tube so there is a need for cell proliferation
in some patients there is excessive neuronal proliferation
What is hemi-megalencephaly?
the bigger hemisphere represents an excess in proliferation
one hemisphere could be too small or too big compared to the other one
What is tuberous sclerosis?
disease of skin and brain
associated with mutations in the tuberous sclerosis genes
TSC 1 or TSC 2
associated with intellectual disability, epilepsy, and autism
What are tuberous sclerosis tumors?
subependymal giant cell astrocytoma (SEGA) are present in 6-14% of patients
these lesions can lead to death
What is microcephaly?
the patient head circumference is normal at birth but then fails to progress normally
What is the FOXG1 gene?
FOXG1 is a member of the forkhead family initially described in flies
mutations in FOXG1 lead to smaller head circumference via several pathways
