Lecture 2 - embryogenesis Flashcards
The CNS is generated by what type of cells?
Pluripotent neuroepithelial stem cells (spindle-shaped)
Interkinetic nuclear migration
Early in the cycle > move superficially
Later > come down to deep surface (VZ)
After interkinetic nuclear migration…
- Neuroepithelial stem cells undergo mitotic division in VZ
- Then we get an increase in progenitor number
- Increase in size until a certain point
When proliferative zone has reached its limit…
Radial Glial cells appear (1st non-mitotic cells)
Radial Glial cells
Neurons travel up radial glial cells and so they can leave deep VZ and differentiate
* These cells are only seen in developing NS
Mantle Zone (MZ)
Neurons leave radial glial cells and accumulate superficially forming MZ
* Next wave will follow same process but jump off earlier and differentiate under previous layer
What happens to VZ as more neurons are generated?
It becomes thinner
* MZ thickens.
Cortical Layer 4
Receives Thalamic projections
* High density of stellates
* Sensory
* Project to 2-3
Cortical Layer 2-3
Intracortical connectivity between areas/layers, across Corpus Cal.
* Small pyramidal cells
* Project down to 5-6
Cortical Layer 5
Main output layer to distant subcortical centres
* Has biggest cells
* Long distance
Cortical Layer 6
Projections to Thalamus
* Relay sensory info
* Output
Cortical Layer 1
Mainly acellular
* Dendrites
Subventricular Zone (SVZ)
Remnant of early embryonic layers
* Lay dormant
* Small no. of stem cells in the adult remain?
Where do cells start to differentiate in corticogenesis?
In the primordial plexiform layer (PPL)
What occurs when the second wave of neurons hop off radial glial cells in corticogenesis?
They leave and split the initial layer of cells into a superficial (Marginal Z) and deep layer (SubP)
* This middle layer will the the cortical plate (CP)
How many layers come from the CP?
All except layer 1
What occurs to subsequent waves following formation of CP
Move up and differentiate superficially.
* MZ > Layer 1
Intermediate zone (IZ)
White matter forming below CP
Do inhibitory neurons travel up radial glial cells?
No, they are generated subcortically and travel tangetially
Excitatory Interneurons
- Glutamatergic
- Travel up Radial Glial
- 80%
Inhibitory Interneurons
- GABAergic
- Forerunner of basal ganglia
- Less tightly controlled (complex and longer migration)
Where do Wnts and BMPs come from?
Caudal and Medial regions
Where do fibroblast growth factors (FGFs) come from?
Rostral regions
Where do Epidermal growth factors (EGFs) come from?
More Lateral regions
What effect does Wnts, BMPs, EGFs, FGFs have?
Act as morphogens and sets up gradients of transcription factors
What are growth cones?
Tip of growing axon
* Have processes that sample enviro
* Decision making
Filopodia
Long, skinny processes on the growth cone
Lamellipodia
Flat processes on the growth cone
Extracellular matrix adhesion
Growth cone must adhere to something for cellular machinary to work (e.g. cell surface)
Fasciculation
Growth cone adhere to axon of another neuron that has already grown further down the pathway
Chemoattraction
Soluble molecule released from signalling centre. Sets up gradient to attract
Contact inhibition
Surface of cells push the growth cone away. Discourage adherence
Chemorepulsion
Molecule is inhibitory to growth of axon
First decision in the retinotectal pathway
RGCs growing on superficial surface of retina need to make a 90° turn into optic nerve head > proper
Second decision in the retinotectal pathway
Occurs at optic chiasm:
* Temporal > stay ipsilateral
* Nasal > cross over contralaterally
What happens when a growth cone needs to make a decision?
- It slows down
- Becomes more complex
- Processes are working
Axons in the optic chiasm
Nasal: crosses midline
Temporal: turns before reaching midline (growth cone that is close to the middle line collapses)
Netrin and its receptors
Soluble
* Receptors: DCC & Unc5
* If DCC + Unc5 present: REPULSION
* Only DDC: ATTRACTION
Slit
Soluble
* Mostly REPULSIVE with Robo
Ephrins
Mostly REPULSIVE with Eph
Mapping of vision
Pass optic chiasm > Superior Collic.
* Nasal axons > caudal part of tectum
* Temporal axons > rostral part of tectum
Why is mapping and decision making so important for binocular vision?
Light hits our eyes in straight lines at different points in the retina.
Need a spacially accurate view
Membrane Stripe Assay
Take cell membranes from rostral and caudal
* Nasal: didn’t show a bias
* Temporal: ONLY grow on the anterior/rostral stripes. Something repelling in the caudal portion?
EphA receptors + ligands in the retinotectal pathway
- Temporal RGCs show high expression of EphA5 (low nasally)
- Caudal Superior Collic. show high amount of ephrin A5 ligand (none rostrally)
Refinement of projections
Early projections are exuberant
Adult - refined
What happens when synapses aren’t effective at driving post-synaptic responses?
They get pruned away and those that are more effective branch and takeover
