NEUS 609 - Oligodendrocytes & Myelin I

silver-carbonate

Oligodendrocytes were named by Del Rio Hortega in the 1920s and discovered using the ____ staining method aka Golgi-Hortega method.

progenitor cells, in vitro

In the 1980s was when the first isolation and long-term oligodendrocyte cultures happened, showing that ___ can develop ___.

specification

neural stem cells develop into oligodendrocyte progenitor cells (OPC) via ____.

migration, proliferation, differentiation, myelination

Oligodendrocyte progenitor cells (OPC) develop into mature oligodendrocytes after: ___, ___, ___, and ___.

oligodendrocyte progenitor cells

___ aka OPCs appear mainly in the ventral midline of the 3rd ventricle and ventral spinal cord (SPC).

floorplate, Shh

OPCs appear in ventral areas of 3rd ventricle and SPC via the specification of neural stem cells, which depends mainly on the ___ development, which itself relies on the molecule ___.

domain, Olig2

The molecule Shh responsible for the floorplate/ventral development of the nervous system create a progenitor ___, which is making somatic motor neurons and THEN oligodendrocytes when exposed to the transcription factor (TF) ___.

ventral

__ development whether in the SPC or Telencephalon is Shh-DEPENDENT and represents the 1st wave of oligodendrocyte development.

dorsal

__ development in SPC is shh-INDEPENDENT and are part of the 2nd wave of oligodendrocyte development.

lateral ganglionic eminences

the dorsal development in the Telencephalon is also Shh-independent and create progenitor cells from ____.

cortex

The 3rd wave of oligodendrocyte development only applies to the telencephalon and creates progenitor cells from the ___.

• Happens mostly after birth

heterogeneity

oligodendrocyte ___ refers to the fact that transcriptionally different oligodendrocytes from different locations have different functions

• due to differences in gene expression

1st

__ wave of oligodendrocytes refers to ventral development which is Shh-DEPENDENT, but also to the guidance of interneurons away from vasculature to the cortex. `

neocortex

dorsal oligodendrocytes are the one to myelinate the ___

unidirectional contact repulsion

The 1st wave of oligodendrocyte development also guides interneurons away from vasculature to the cortex using ____.

female

__ mice

• HIGHER cell migration and proliferation properties

• LESS efficient myelination

Basically, more progenitors made but they are less efficient at myelinating.

male

__ mice

• HIGHER cell differentiation and myelination properties

chemical cues

OPCs migrate based on soluble ____, such as Netrin which repel OPCs

• repulsive cues in higher concentrations closer to the site of origin to force OPCs outward

• attractive cues closer to the target area

migrating

oligodendrocyte progenitor cells (OPCs) are proliferating AT THE SAME TIME AS they are ___.

mitogenic

proliferation is dependent on the availability of ___ factors

PDGF, bFGF

oligodendrocyte proliferation is driven by ___ and ___.

platelet-derived growth factor

PDGF

• drives oligodendrocytes proliferation

• mitogenic factor

bFGF

basic fibroblast growth factor

• drives oligodendrocytes proliferation

• mitogenic factor

neuroepithelium

OPCs appear in specific regions of the ___ during development.

galactocerebroside

aka Galc

expressed in IMMATURE oligodendrocytes

myelin basic protein

aka MBP

expressed in MATURE oligodendrocytes

proteolipid protein

aka PLP

expressed in MATURE oligodendrocytes

mature oligodendrocytes markers

• MBP

• PLP

A2B5

cell surface ganglioside

• markers for OPCs

NG2

chondroitin sulfate proteoglycan co-expressed with PDGF alpha receptor

• markers of OPCs

PDGFaR

platelet-derived growth factor receptor, co-expressed with NG2

• markers of OPCs

markers of oligodendrocyte progenitor cells (OPCs)

• A2B5

• NG2

• PDGFaR

O1, O4

cell surface glycolipids

• markers for IMMATURE oligodendrocytes

immature oligodendrocytes markers

• Galc

• O1

• O4

premyelinating

oligodendrocyte morphology

radial and symmetrical extension of processes

NO CONTACT with axons

transitional premyelinating

oligodendrocyte morphology

processes start to myelinate

SOME CONTACT with axons

myelinating

oligodendrocyte morphology

ALL processes are in contact with axons

immature, premyelinating

oligodendrocytes EXIT CELL CYCLE when they become ___/at the ___ stage.

without

oligodendrocytes CAN differentiate into mature state ___ axonal presence

T3

thyroid hormone driving and accelerating oligodendrocyte differentiation to timely and efficiently produce myelin

• KO leads to myelination deficit

epigenetic

oligodendrocyte differentiation is also regulated by ___ which is a form of INTRINSIC regulation

• acylation = loose chromatin = gene expression

• methylation = tight chromatin = no gene access

inhibitor TFs of oligodendrocyte differentiation

• Hes5

• Id2/4

• Sox 5/6

promoter TFs of oligodendrocyte differentiation

• MyRf

• Olig2

• Sox10

MyRF

transcription factor (TF) promoting oligodendrocyte differentiation

• KO causes hypomyelination

natural cell death, excess

The FINAL number of oligodendrocytes is regulated via ____.

• progenitors are made in ___ and attachment to axons is what determine their survival.

type 2

oligodendrocytes can differentiate into ___ astrocytes upon chromic disease or injury

stepwise

oligodendrocytes differentiation occurs in a ___ progression from OPCs to maturity.

adult

OPCs remain present in the __ brain