Oligodendrocytes

Question 1

Describe the origin of oligodendrocyte precursor cells (OPCs)

Answer 1

neuroepithelium -> CNS -> neural tube fusion -> SVZ cells -> OPCs

Question 2

What arises from OPCs?

Answer 2

• oligodendrocytes
• astrocytes

(in culture: both
in body: more oligodendrocyte)

Question 3

Key marker of oligodendrocyte precursors?

Answer 3

PDGF-alpha receptor

Question 4

Relationship between PDGF-ar and O-2A cells?

Answer 4

Type 1 astrocytes secrete PDGF (PDGF-AA and BB), which is received by O-2A cells (via PDGFalphaalpha receptor)

Question 5

Where does PDGFaR cell foci first appear?

Answer 5

Ventral spinal cord (in ventricular zone)

Question 6

What is Olig2?

Answer 6

General marker for oligodendrocyte lineage. A basic helix-loop-helix transcription factor

Question 7

Role of the notochord w/ oligodendrocytes?

Answer 7

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

Question 8

How is there cell type specification for oligodendrocytes?

Answer 8

Morphogenic gradients (SHH/BMP4) -> these activate diff t.factors depending on diff morphogen conc.s -> specifies cell types

Question 9

Describe mechanism of opposing morphogenic gradients for oligodendrocytes

Answer 9

Notochord (floor plate) produces SHH (diffuses up like a hedgehog spine)
Ectoderm (roof plate) produces BMP4 (diffuses downward)

Question 10

Role of Olig1?

Answer 10

Not essential for OPC production BUT required for maturation (marker = MBP) into oligodendrocytes

KO: OPCs present + contact but don’t myelinate axons

Question 11

Role of Olig2?

Answer 11

Required for oligodendrocytes in spinal cord

Question 12

Effect of SHH?

Answer 12

Promotes oligodendrocyte development

Question 13

Effect of (bone morphogenic protein 4) BMP4?

Answer 13

Inhibits oligodendrocyte development

Question 14

Effect of SHH and BMP4 on astrocytes?

Answer 14

none

Question 15

How do OPCs move to target site?

Answer 15

Pushed along axons by Netrin-1 and Semma3a

Question 16

Factors involved in oligodendrocyte proliferation?

Answer 16

PDGF
FGF2
Neuregulin beta-1

Question 17

Effect of PDGF on oligodendrocytes?

Answer 17

Increased proliferation (dose-dose dependent)

Once PDGF decreases -> differentiation occurs

Question 18

Effect of FGF2 on oligodendrocytes?

Answer 18

• Increased proliferation
• Increased migration
• Decreased differentiation

Question 19

Effect of neuregulin beta-1 on oligodendrocytes?

Answer 19

• Increased proliferation

- increased differentiation

Question 20

Factors involved in oligodendrocyte differentiation?

Answer 20

• YY1
• Myelin Gene Regulatory Factor (MRF)
• Olig1/2 (activators)
• Sox5 (inhibitor)

Question 21

Effect of Ying Yan 1 (YY1)

Answer 21

Represses transcriptional inhibitors of myelin gene (inhibits the inhibitors)

Question 22

What is MRF and outcome of its KO?

Answer 22

CNS-specific nuclear protein expressed only in post-mitotic oligogendrocytes

KO: decreased myelin gene exp -> No CNS myelin -> ataxia

Question 23

Relevance of axonal contact?

Answer 23

Required for oligodendrocyte survival (without input, cell dies by apoptosis)

[prevents overproduced cell survival]

Question 24

How oligodendrocytes initiate axonal contact?

Answer 24

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

Question 25

How do oligodendrocyte processes locate axons?

Answer 25

Axons express survival signals e.g. NCAM. NCAM binds to same protein on olig process -> Ig-Ig interaction -> conform change -> cell survival signal

Question 26

Overview of mechanisms that trigger myelination

Answer 26

- electrical activity in axon - NCAM on axon stimulates survival - inhib molecules downregulation (PSA-NCAM) - axo-glial signals promote myelination

Question 27

How electrical activity in axon triggers myelination?

Answer 27

Electrical activity -> ATP release -> astrocytes secrete LIF -> LIF promotes olig survival

Question 28

Describe the physical process of myelination

Answer 28

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

Question 29

[during myelination] | How do end loops of oligodendrocyte adhere to axonal membrane

Answer 29

NF155 and Caspr-1

Question 30

How are nodes of Ranvier formed?

Answer 30

[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+)

Question 31

Myelin structure: what are the dark lines and lighter lines composed of?

Answer 31

Dark lines: compacted intracellular faces of membrane (protein rich) Lighter lines: compacted extracellular faces of the membrane

Question 32

How is myelin remodelling possible in an adult CNS?

Answer 32

OPCs continue to proliferate and generage myelinating oligodendrocytes [role in learning]