Basics of Brain Development Flashcards
What is the embryo called at day 4, before blastulation?
Morula
What is the embryo become during blastulation and when does this occur?
▪️ Blastula followed by a blastocyst
▪️ From ~day 5-6 to day 21 (3 weeks)
What is the blastocysts made up of?
▪️ Trophoblast - outer layer
▪️ Inner cell mass
▪️ Blastocoel
What does the inner cell mass of the blastocyst become?
▪️ Hypoblast
▪️ Epiblast
Which part of the inner cell mass differentiates into the ectoderm, mesoderm, and endoderm?
The epiblast
When does gastrulation occur?
3 weeks post conception (E13)
What happens during gastrulation?
▪️ The blastocyst becomes a multidimensional layered structures
▪️ Formation of the ectoderm, mesoderm, and endoderm
▪️ Ectoderm differentiates into skin and the neural plate
What happens if gastrulation goes wrong?
Conjoined twins
Where do the microglia come from and when do they arrive in the brain?
The mesoderm
Arrive in the brain via circulation around day 28
What happens to cell division around day 25?
▪️ Symmetrical
▪️ Producing neural progenitor cells
Which cells of the ectoderm differentiate into skin and why?
▪️ Ventral cells
▪️ BMP-4 binds to them
Which cells of the ectoderm form the neural plate and why?
▪️ Dorsal cells
▪️ The organiser on the ventral side releases chordin and noggin which prevent BMP-4 from binding
What are the main roles of microglia during neurodevelopment?
▪️ Phagocytosis
▪️ Formation and guidance of axons to white matter
▪️ Organisation of the nervous system
▪️ Neurogenesis, synaptogenesis, and synaptic pruning
When does gastrulation end?
Day 28
What condition occurs during gastrulation if an individual has one copy of the CSF1R gene mutation?
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
▪️ WM abnormalities
▪️ Myelin loss
▪️ Cognitive and motor problems
What happens during gastrulation if someone has two copies of the CSF1R gene mutation?
▪️ No microglia
▪️ Corpus callosum agenesis
▪️ Disorganised brain
(poor prognosis)
When does neurulation start?
Day 22
What happens to the neural plate during neurulation?
It folds together, from the middle outwards, forming the neural tube
When does the rostral part of the neural tube close and what happens if this is incomplete?
▪️ At the beginning of week 4
▪️ Incomplete closure = ancephaly
When does the caudal part of the neural tube close and what happens if this is incomplete?
▪️ End of week 4
▪️ Spina bifida
What does the neural tube form when it is fully closed?
3 vesicles:
▪️ Prosencephalon (forebrain)
▪️ Mesencephalon (midbrain)
▪️ Rhombencephalon (hind brain)
What happens to cell division around day 42?
▪️ Becomes asymmetrical
▪️ Regulated by Notch pathway
What type of brain cell is created first and how?
▪️ Neurons
▪️ Progenitor cells express proneural genes
▪️ Accumulation of proneural proteins
What brain cells are created second and how?
▪️ Glia (astrocytes first followed by oligodendrocytes)
▪️ Proneural genes are inhibited by the Notch pathway
Where does brain cell differentiation mainly occur?
In the ventricular zone of the neural tube
What is the first step of neuronal migration and what happens during this?
▪️ Somal translocation
▪️ Basal processes of Cajal-Retzius cells attach to pial surface of the embryonic cortex and pull themselves up
What is the main disorder of neuronal migration onset?
Schizencephaly (split brain)
▪️ EMX2 mutation
▪️ Cleft forms in brain
▪️ Enlarged ventricles, developmental delay
What happens when the cells reach the pial surface?
They split the preplate forming the marginal layer (where they settle), the cortical plate, and the subplate
What causes the Cajal-Retzius cells to stop migrating when they reach the pial and what layer do they form?
▪️ Migration stopped by reelin
▪️ Form the marginal layer
How do glial cells migrate?
Move up (radially), leaving their body behind
What is radial glial migration?
▪️ Neurons migrate via the glia
▪️ Start in the ventricular zone
▪️ Settle inside out, first forming layer 6, then 5, then 4 etc….
What part of the embryonic cortex forms the cortical grey matter?
The cortical plate
(Between subplate and marginal layer)
What part of the embryonic cortex forms the white matter?
The intermediate zone
(Above ventricular by below subplate)
What are the two main types of neuronal migration?
▪️ Radial
▪️ Tangential
What is tangential migration?
Neurons from the ventral telencephalon move tangentially into the cortical plate via inhibitory interneurons
How many layers are there in the cortical plate and what is the significance of these?
▪️ 6 layers (1=top)
▪️ Cells in different layers have different intrinsic characteristics
▪️ Differentiate later to become specialised
How were the layers of the cortical plate first discovered?
With thymidine in pregnant mice
What is the main disorder of ongoing migration?
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
What is the main disorder of migration stopping?
Type 2 Lissencephaly
▪️ FCMD mutation
▪️ Cells clump and misalign at pial surface resulting in cobblestone brain
▪️ Developmental delay, hypotonia, ocular abnormalities
What are the main stages of neuron differentiation?
- Neuronal polarisation
- Axon formation
- Dendritic formation
- Maturation
What grows from the cell body in the polarisation stage of neuron differentiation?
Actin-rich protrusion
What does the axon originate from?
The growth cone
When does myelination begin and end?
Week 24, ending around age 18
What percentage of neurons die prenatally and why?
▪️ ~50%
▪️ Apoptosis
▪️ Disappearance of the marginal zone and subplate
▪️ Removal of any that do not establish connections
(neurotrophic hypothesis!)
What are the two areas of postnatal neuron production?
▪️ Subventricular zone
▪️ Dentate gyrus of the hippocampus
What aspects of maternal environment may effect developmental outcome?
▪️ Alcohol consumption during pregnancy
▪️ Drug use
▪️ Maternal hypoxia
▪️ Maternal immune system (transfer of antibodies, activation of microglia)
