Oligodendrocytes Flashcards
Describe the origin of oligodendrocyte precursor cells (OPCs)
neuroepithelium -> CNS -> neural tube fusion -> SVZ cells -> OPCs
What arises from OPCs?
- oligodendrocytes
- astrocytes
(in culture: both
in body: more oligodendrocyte)
Key marker of oligodendrocyte precursors?
PDGF-alpha receptor
Relationship between PDGF-ar and O-2A cells?
Type 1 astrocytes secrete PDGF (PDGF-AA and BB), which is received by O-2A cells (via PDGFalphaalpha receptor)
Where does PDGFaR cell foci first appear?
Ventral spinal cord (in ventricular zone)
What is Olig2?
General marker for oligodendrocyte lineage. A basic helix-loop-helix transcription factor
Role of the notochord w/ oligodendrocytes?
Notochord is essential for OPCs and motor neurons (as they share the same progenitors)
NB: mouse lacking notochord/floor plate -> no OPCs or motor neurons
How is there cell type specification for oligodendrocytes?
Morphogenic gradients (SHH/BMP4) -> these activate diff t.factors depending on diff morphogen conc.s -> specifies cell types
Describe mechanism of opposing morphogenic gradients for oligodendrocytes
Notochord (floor plate) produces SHH (diffuses up like a hedgehog spine)
Ectoderm (roof plate) produces BMP4 (diffuses downward)
Role of Olig1?
Not essential for OPC production BUT required for maturation (marker = MBP) into oligodendrocytes
KO: OPCs present + contact but don’t myelinate axons
Role of Olig2?
Required for oligodendrocytes in spinal cord
Effect of SHH?
Promotes oligodendrocyte development
Effect of (bone morphogenic protein 4) BMP4?
Inhibits oligodendrocyte development
Effect of SHH and BMP4 on astrocytes?
none
How do OPCs move to target site?
Pushed along axons by Netrin-1 and Semma3a
Factors involved in oligodendrocyte proliferation?
PDGF
FGF2
Neuregulin beta-1
Effect of PDGF on oligodendrocytes?
Increased proliferation (dose-dose dependent)
Once PDGF decreases -> differentiation occurs
Effect of FGF2 on oligodendrocytes?
- Increased proliferation
- Increased migration
- Decreased differentiation
Effect of neuregulin beta-1 on oligodendrocytes?
- Increased proliferation
- increased differentiation
Factors involved in oligodendrocyte differentiation?
- YY1
- Myelin Gene Regulatory Factor (MRF)
- Olig1/2 (activators)
- Sox5 (inhibitor)
Effect of Ying Yan 1 (YY1)
Represses transcriptional inhibitors of myelin gene (inhibits the inhibitors)
What is MRF and outcome of its KO?
CNS-specific nuclear protein expressed only in post-mitotic oligogendrocytes
KO: decreased myelin gene exp -> No CNS myelin -> ataxia
Relevance of axonal contact?
Required for oligodendrocyte survival (without input, cell dies by apoptosis)
[prevents overproduced cell survival]
How oligodendrocytes initiate axonal contact?
Developing oligodendrocytes extend many radial processes to contact axons ->
- those that do not contact are withdrawn
- if no contact with any axons -> apoptosis
- axonal contact -> myelination
How do oligodendrocyte processes locate axons?
Axons express survival signals e.g. NCAM.
NCAM binds to same protein on olig process -> Ig-Ig interaction -> conform change -> cell survival signal
Overview of mechanisms that trigger myelination
- electrical activity in axon
- NCAM on axon stimulates survival
- inhib molecules downregulation (PSA-NCAM)
- axo-glial signals promote myelination
How electrical activity in axon triggers myelination?
Electrical activity -> ATP release -> astrocytes secrete LIF -> LIF promotes olig survival
Describe the physical process of myelination
Oligodendrocyte process contacts axon and leading process tucks under previously deposited membrane
Cytoplasm restricted to tighten this structure (end loops adhere to axon membrane)
Wrapping and lateral extension
[during myelination]
How do end loops of oligodendrocyte adhere to axonal membrane
NF155 and Caspr-1
How are nodes of Ranvier formed?
[triggered by myelination]
Clustering of Na+ channels -> STOP signal -> forms node of Ranvier
Myelin stops the current leakage by segregating ion channels (nodal Na+, paranodal K+)
Myelin structure: what are the dark lines and lighter lines composed of?
Dark lines: compacted intracellular faces of membrane (protein rich)
Lighter lines: compacted extracellular faces of the membrane
How is myelin remodelling possible in an adult CNS?
OPCs continue to proliferate and generage myelinating oligodendrocytes
[role in learning]
