Basics of Brain Development

Question 1

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

Answer 1

Morula

Question 2

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

Answer 2

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

Question 3

What is the blastocysts made up of?

Answer 3

▪️ Trophoblast - outer layer
▪️ Inner cell mass
▪️ Blastocoel

Question 4

What does the inner cell mass of the blastocyst become?

Answer 4

▪️ Hypoblast
▪️ Epiblast

Question 5

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

Answer 5

The epiblast

Question 6

When does gastrulation occur?

Answer 6

3 weeks post conception (E13)

Question 7

What happens during gastrulation?

Answer 7

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

Question 8

What happens if gastrulation goes wrong?

Answer 8

Conjoined twins

Question 9

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

Answer 9

The mesoderm

Arrive in the brain via circulation around day 28

Question 10

What happens to cell division around day 25?

Answer 10

▪️ Symmetrical
▪️ Producing neural progenitor cells

Question 11

Which cells of the ectoderm differentiate into skin and why?

Answer 11

▪️ Ventral cells
▪️ BMP-4 binds to them

Question 12

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

Answer 12

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

Question 13

What are the main roles of microglia during neurodevelopment?

Answer 13

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

Question 14

When does gastrulation end?

Answer 14

Day 28

Question 15

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

Answer 15

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

▪️ WM abnormalities
▪️ Myelin loss
▪️ Cognitive and motor problems

Question 16

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

Answer 16

▪️ No microglia
▪️ Corpus callosum agenesis
▪️ Disorganised brain

(poor prognosis)

Question 17

When does neurulation start?

Answer 17

Day 22

Question 18

What happens to the neural plate during neurulation?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

▪️ End of week 4
▪️ Spina bifida

Question 21

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

Answer 21

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

Question 22

What happens to cell division around day 42?

Answer 22

▪️ Becomes asymmetrical
▪️ Regulated by Notch pathway

Question 23

What type of brain cell is created first and how?

Answer 23

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

Question 24

What brain cells are created second and how?

Answer 24

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

Question 25

Where does brain cell differentiation mainly occur?

Answer 25

In the ventricular zone of the neural tube

Question 26

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

Answer 26

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

Question 27

What is the main disorder of neuronal migration onset?

Answer 27

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

Question 28

What happens when the cells reach the pial surface?

Answer 28

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

Question 29

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

Answer 29

▪️ Migration stopped by reelin ▪️ Form the marginal layer

Question 30

How do glial cells migrate?

Answer 30

Move up (radially), leaving their body behind

Question 31

What is radial glial migration?

Answer 31

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

Question 32

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

Answer 32

The cortical plate (Between subplate and marginal layer)

Question 33

What part of the embryonic cortex forms the white matter?

Answer 33

The intermediate zone (Above ventricular by below subplate)

Question 34

What are the two main types of neuronal migration?

Answer 34

▪️ Radial ▪️ Tangential

Question 35

What is tangential migration?

Answer 35

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

Question 36

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

Answer 36

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

Question 37

How were the layers of the cortical plate first discovered?

Answer 37

With thymidine in pregnant mice

Question 38

What is the main disorder of ongoing migration?

Answer 38

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

Question 39

What is the main disorder of migration stopping?

Answer 39

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

Question 40

What are the main stages of neuron differentiation?

Answer 40

1. Neuronal polarisation 2. Axon formation 3. Dendritic formation 4. Maturation

Question 41

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

Answer 41

Actin-rich protrusion

Question 42

What does the axon originate from?

Answer 42

The growth cone

Question 43

When does myelination begin and end?

Answer 43

Week 24, ending around age 18

Question 44

What percentage of neurons die prenatally and why?

Answer 44

▪️ ~50% ▪️ Apoptosis ▪️ Disappearance of the marginal zone and subplate ▪️ Removal of any that do not establish connections (neurotrophic hypothesis!)

Question 45

What are the two areas of postnatal neuron production?

Answer 45

▪️ Subventricular zone ▪️ Dentate gyrus of the hippocampus

Question 46

What aspects of maternal environment may effect developmental outcome?

Answer 46

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