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NEURO 210 > Lecture 4: Brain Embryology > Flashcards

Lecture 4: Brain Embryology Flashcards

1
Q

Why is studying brain development important?

A

a defect in brain development can cause epilepsy, learning disability, intellectual disability, autism spectrum disorder, brain cancer

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2
Q

What is the oldest way of looking at the brain?

A

pathology

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3
Q

What brain imaging techniques are used when studying brain embryology?

A

pathology and MRI shows us what happens to the brain development

genetics is useful to understanding what causes the normal and abnormal behavior

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4
Q

What are the genomic methods used when studying brain embryology?

A

karyotype

CGH

next-generation sequencing

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5
Q

What are the major steps in the development of the brain?

A

gastrulation

primary neurulation

porencephalic development

neuronal proliferation

neuronal migration

organization

myelination

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6
Q

What is gastrulation?

A

formation of three layers of cells

endoderm (inside)
mesoderm (middle)
ectoderm (exterior, neuron, skin)

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7
Q

What is neurulation?

A

neurulation refers to formation of the neural tube from a flat layer of ectodermal cells

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8
Q

What are the important genes in neurulation?

A

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

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9
Q

What is neural tube closure?

A

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

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10
Q

What is anencephaly?

A

defect of anterior neuropore closure

result in anencephaly

this type of lesion is frequently not compatible with life

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11
Q

What is spina bifida?

A

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

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12
Q

What is prosencephalic development?

A

the anterior part of the neural tube splits into 2 prosencephalic vesicles

starts to look more like two hemispheres

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13
Q

What is holoprosencephaly?

A

failure of cleavage of the 2 hemispheres

lack of separation of the two hemisphere

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14
Q

What genes are associated with holoprosencephaly?

A

the sonic hedgehog pathway (SHH) pathway

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15
Q

What is the SHH pathway?

A

the SHH pathways involves the patched and smoothened receptors and the secondary messenger GLI that results in transcription of DNA and proliferation

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16
Q

What occurs around 2 weeks of gestation?

A

the formation of the brainstem

17
Q

What is mobius syndrome?

A

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

18
Q

What are homeobox (HOX) genes?

A

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

19
Q

What is neuronal proliferation?

A

the brain is thicker than a tube so there is a need for cell proliferation

in some patients there is excessive neuronal proliferation

20
Q

What is hemi-megalencephaly?

A

the bigger hemisphere represents an excess in proliferation

one hemisphere could be too small or too big compared to the other one

21
Q

What is tuberous sclerosis?

A

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

22
Q

What are tuberous sclerosis tumors?

A

subependymal giant cell astrocytoma (SEGA) are present in 6-14% of patients

these lesions can lead to death

23
Q

What is microcephaly?

A

the patient head circumference is normal at birth but then fails to progress normally

24
Q

What is the FOXG1 gene?

A

FOXG1 is a member of the forkhead family initially described in flies

mutations in FOXG1 lead to smaller head circumference via several pathways

25
Q

What is cell migration?

A

the human cortex is formed is organized into 6 layers of neurons

the neurons are born in the periventricular zone and then need to migrate out toward the brain surface along guides (on the progenitor cells which become differentiated into glial)

this is known as inside out migration

26
Q

What does defective cell migration result in?

A

defective neuronal migration results in neurons staying close to the ventricles

27
Q

What is periventricular nodular heterotropia?

A

patients can suffer from epilepsy cognitive dysfunction

caused by genetic mutation: Filamin 1 (X), ARFGEF 2 (20q), Elastin (Williams syndrome), fragile X syndrome

28
Q

What is lissencephaly?

A

smooth brain

can result from abnormal migration

29
Q

What genes are associated with cell migration?

A

they regulate how cells can attach and detach

LIS 1

14-3-3 varepsilon

doublecortin

reelin

ARX

30
Q

What is neurite outgrowth?

A

dendrites and axon develop over time leading to an increase in the neuron arborization

31
Q

What is spines development?

A

synapses are formed at the tip of the dendrites on a structure named spine

32
Q

What are some diseases associated with abnormal dendritic arbor/spine?

A

down syndrome

fragile X syndrome

Angelman syndrome

other intellectual disabilities (ID) and autism spectrum disorders (ASD)

33
Q

What is fragile X syndrome?

A

most common ID in males

dysmorphic features

autism (60%)

epilepsy (30%)

caused by mutation in Fragile X gene leading to absence of Fragile X protein

34
Q

What is the abnormal circuit associated with Fragile X?

A

examination of the brain of flies, mice, and humans with Fragile X revealed an excess of long thin dendritic spines

memory defect also linked to Fragile X

35
Q

What is glia proliferation?

A

there is 1 1/2 glia cell for each neuron

transformation of the guide cells into glia

recycling of glutamate into glutamine

regulation of calcium flux in neurons

36
Q

What is myelination?

A

myelin allows saltatory conduction and increased speed

myelin develops progressively with age

NEURO 210 (23 decks)

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