Basics of Brain Development Flashcards

1
Q

What is the embryo called at day 4, before blastulation?

A

Morula

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2
Q

What is the embryo become during blastulation and when does this occur?

A

▪️ Blastula followed by a blastocyst
▪️ From ~day 5-6 to day 21 (3 weeks)

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3
Q

What is the blastocysts made up of?

A

▪️ Trophoblast - outer layer
▪️ Inner cell mass
▪️ Blastocoel

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4
Q

What does the inner cell mass of the blastocyst become?

A

▪️ Hypoblast
▪️ Epiblast

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5
Q

Which part of the inner cell mass differentiates into the ectoderm, mesoderm, and endoderm?

A

The epiblast

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6
Q

When does gastrulation occur?

A

3 weeks post conception (E13)

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7
Q

What happens during gastrulation?

A

▪️ The blastocyst becomes a multidimensional layered structures
▪️ Formation of the ectoderm, mesoderm, and endoderm
▪️ Ectoderm differentiates into skin and the neural plate

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8
Q

What happens if gastrulation goes wrong?

A

Conjoined twins

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9
Q

Where do the microglia come from and when do they arrive in the brain?

A

The mesoderm

Arrive in the brain via circulation around day 28

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10
Q

What happens to cell division around day 25?

A

▪️ Symmetrical
▪️ Producing neural progenitor cells

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11
Q

Which cells of the ectoderm differentiate into skin and why?

A

▪️ Ventral cells
▪️ BMP-4 binds to them

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12
Q

Which cells of the ectoderm form the neural plate and why?

A

▪️ Dorsal cells
▪️ The organiser on the ventral side releases chordin and noggin which prevent BMP-4 from binding

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13
Q

What are the main roles of microglia during neurodevelopment?

A

▪️ Phagocytosis
▪️ Formation and guidance of axons to white matter
▪️ Organisation of the nervous system
▪️ Neurogenesis, synaptogenesis, and synaptic pruning

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14
Q

When does gastrulation end?

A

Day 28

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15
Q

What condition occurs during gastrulation if an individual has one copy of the CSF1R gene mutation?

A

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

▪️ WM abnormalities
▪️ Myelin loss
▪️ Cognitive and motor problems

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16
Q

What happens during gastrulation if someone has two copies of the CSF1R gene mutation?

A

▪️ No microglia
▪️ Corpus callosum agenesis
▪️ Disorganised brain

(poor prognosis)

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17
Q

When does neurulation start?

A

Day 22

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18
Q

What happens to the neural plate during neurulation?

A

It folds together, from the middle outwards, forming the neural tube

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19
Q

When does the rostral part of the neural tube close and what happens if this is incomplete?

A

▪️ At the beginning of week 4
▪️ Incomplete closure = ancephaly

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20
Q

When does the caudal part of the neural tube close and what happens if this is incomplete?

A

▪️ End of week 4
▪️ Spina bifida

21
Q

What does the neural tube form when it is fully closed?

A

3 vesicles:
▪️ Prosencephalon (forebrain)
▪️ Mesencephalon (midbrain)
▪️ Rhombencephalon (hind brain)

22
Q

What happens to cell division around day 42?

A

▪️ Becomes asymmetrical
▪️ Regulated by Notch pathway

23
Q

What type of brain cell is created first and how?

A

▪️ Neurons
▪️ Progenitor cells express proneural genes
▪️ Accumulation of proneural proteins

24
Q

What brain cells are created second and how?

A

▪️ Glia (astrocytes first followed by oligodendrocytes)
▪️ Proneural genes are inhibited by the Notch pathway

25
Q

Where does brain cell differentiation mainly occur?

A

In the ventricular zone of the neural tube

26
Q

What is the first step of neuronal migration and what happens during this?

A

▪️ Somal translocation
▪️ Basal processes of Cajal-Retzius cells attach to pial surface of the embryonic cortex and pull themselves up

27
Q

What is the main disorder of neuronal migration onset?

A

Schizencephaly (split brain)
▪️ EMX2 mutation
▪️ Cleft forms in brain
▪️ Enlarged ventricles, developmental delay

28
Q

What happens when the cells reach the pial surface?

A

They split the preplate forming the marginal layer (where they settle), the cortical plate, and the subplate

29
Q

What causes the Cajal-Retzius cells to stop migrating when they reach the pial and what layer do they form?

A

▪️ Migration stopped by reelin
▪️ Form the marginal layer

30
Q

How do glial cells migrate?

A

Move up (radially), leaving their body behind

31
Q

What is radial glial migration?

A

▪️ Neurons migrate via the glia
▪️ Start in the ventricular zone
▪️ Settle inside out, first forming layer 6, then 5, then 4 etc….

32
Q

What part of the embryonic cortex forms the cortical grey matter?

A

The cortical plate

(Between subplate and marginal layer)

33
Q

What part of the embryonic cortex forms the white matter?

A

The intermediate zone

(Above ventricular by below subplate)

34
Q

What are the two main types of neuronal migration?

A

▪️ Radial
▪️ Tangential

35
Q

What is tangential migration?

A

Neurons from the ventral telencephalon move tangentially into the cortical plate via inhibitory interneurons

36
Q

How many layers are there in the cortical plate and what is the significance of these?

A

▪️ 6 layers (1=top)
▪️ Cells in different layers have different intrinsic characteristics
▪️ Differentiate later to become specialised

37
Q

How were the layers of the cortical plate first discovered?

A

With thymidine in pregnant mice

38
Q

What is the main disorder of ongoing migration?

A

Type 1 Lissencephaly
▪️ LIS1 and DCX mutation (microtubule)
▪️ Not enough tissue generated resulting in smooth brain and enlarged ventricles
▪️ Low IQ/ID and cognitive impairment

39
Q

What is the main disorder of migration stopping?

A

Type 2 Lissencephaly
▪️ FCMD mutation
▪️ Cells clump and misalign at pial surface resulting in cobblestone brain
▪️ Developmental delay, hypotonia, ocular abnormalities

40
Q

What are the main stages of neuron differentiation?

A
  1. Neuronal polarisation
  2. Axon formation
  3. Dendritic formation
  4. Maturation
41
Q

What grows from the cell body in the polarisation stage of neuron differentiation?

A

Actin-rich protrusion

42
Q

What does the axon originate from?

A

The growth cone

43
Q

When does myelination begin and end?

A

Week 24, ending around age 18

44
Q

What percentage of neurons die prenatally and why?

A

▪️ ~50%
▪️ Apoptosis
▪️ Disappearance of the marginal zone and subplate
▪️ Removal of any that do not establish connections

(neurotrophic hypothesis!)

45
Q

What are the two areas of postnatal neuron production?

A

▪️ Subventricular zone
▪️ Dentate gyrus of the hippocampus

46
Q

What aspects of maternal environment may effect developmental outcome?

A

▪️ Alcohol consumption during pregnancy
▪️ Drug use
▪️ Maternal hypoxia
▪️ Maternal immune system (transfer of antibodies, activation of microglia)

47
Q

Increased dendritic spine is seen in?

A

ASD

48
Q

Decreased dendritic spine is seen in?

A

AD & SZ