Birthday of a neuron
When the cell that differentiates into the neuron undergoes it’s last mitotic division
What are the 3 primary vesicles in brain development?
- Forebrain
- Midbrain
- Hindbrain
What are the 5 secondary vesicles in brain development?
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
1 & 2 are made from the forebrain, 3 is made from the midbrain, and 4 & 5 are made from the hindbrain
How many cells does the human brain have?
~170 billion cells (an equal number of neurons and glia cells)
Neural stem cells (NSCs) differentiate into…
2 things primarily
- Radial glia, which differentiate into neurons, oligodendrocytes, or astrocytes.
- Ependymal cells which secrete spinal fluid and detect changes in the spinal fluids
EMPs (stem cells from the yolk sac) differentiate into…
Macrophage –> microglia involved in the immune system
What are the 2 functions of radial glia?
- neuronal stem cells - capable of self renewal and multipotent generation of neurons and glia.
- Scaffold - allow for proper migration of NPCs and newborn cells as the brain is growing
The two functions of glial cells are…
- holding everything together structurally
2. myelination
Function of oligodendrocytes and Schwann cells
- oligodendricytes are in the CNS and Schwann cells are in the PNS
- wrap around a neuron to make a myelin sheath
- this helps prevent electric dispersion and facilitates
conduction
- this helps prevent electric dispersion and facilitates
Astrocytes (3 functions)
- The blood brain barrier - prevents some things from the PNS from getting into the CNS
- Respond to inflammation in the CNS
- Support synapse homeostasis and neuronal transmission (electrical potential)
Microglia development
Arise from stem cells in the CNS (not neuronal epithelial cells)
From the yolk sac (EMPs)
Migrate from the yolk sac to the CNS before the blood brain barrier closes.
4 functions of microglia
- immunity - inflammation and phagocytosis
- embryogenesis - modulate cell # and wiring
- postnatal development -synapse development
- adulthood - involved in neurodegenerative diseases
What are the 3 zone patterns in the spine?
- ventricular zone - next to the lumen, continue to divide in order to form the next layer
- Mantle (intermediate zone) - grey matter, contains cell bodies.
- Marginal zone (outer) - white matter, comprised of myelinated axons and a few neuronal cell bodies
Which side of the spinal cord gets sensory input?
Dorsal
which side of the spinal cord distributes motor functions?
Ventral
How is the cerebellum organized? (written inner –> outer)
- Ventricular zone
- Mantle zone
- Bergmann Glia
- Internal granule layer - made by BMP signalling
- Purkinje layer - secrete Shh which are involved in the division of granule cells
- Marginal zone
- Outer granule layer
What will happen if SHOX2 is knocked out?
there will be a decrease in Shh therefore there will be a large amount of BMPs so migration and differentiation will begin early. Loss of proper motor control due to improper cerebellum development
How is Shh involved in brain development?
Shh promotes proliferation of granular cells
How are BMPs involved in brain development?
After Shh is done with proliferation, BMPs promote differentiation and migration of cells to their proper place
What is the layout of the cerebral cortex? (from the ventricle to the molecular layer, 6)
- Ventricular zone
- Sub-ventricular zone
- Mantle zone
- Cortical plate
- Marginal zone
- Molecular layer
What order does the cerebral cortex develop?
inside out. ie, layer 6 then layer 5 and so on
What molecule is used for birth-dating a neuron?
3H-thymidine
- it marks all mitotic cells during S phase
- staining fades as the cell divides more
- you’ll find neurons born first will be closer to the inside and neurons born later will be along the edge
How to newborn neurons migrate?
They lose their adhesion molecules for the germinal layer cells and gain adhesion molecules (like Reelin) that attach it to the glia to migrate, the direction it migrates in is regulated by paracrine factors (like BDNF)
If a daughter cell receives more of a certain molecule it will remain a stem cell. Which molecule is this and why doe it remain a stem cell?
- More Par-3 causes the daughter cell to be a stem cell
- due to higher Notch signalling it remains attached to the ventricular zone
- the daughter cell with less Par-3 and less Notch signalling will migrate away to become a neuron
