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BIOL 458
Lecture 6
22
Biology
Undergraduate 4
01/28/2014

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Term
How does Glia compare with Neurons in terms of numbers?
Definition
There is much more Glia than neurons
Term
Which type of neural cells does the PNS give rise to? CNS give rise to?
Definition

Neural crest cells

- neurons

- Schwann cells (peripheral glia) 

 

CNS

- Radial glia (development)

- Ventricular zone cells (Development and Adult) 

---> Neurons, Astrocytes, Oligodendrocytes

 

- Microglia

CNS macrophages (mesodermal derivatives) 

 

Glia are the non-nueronal neural cells 

Term

What doesthe Radial glia provide? 

 

What does the Ventricular Zone cells provide? 

Definition

• neural progenitor cell during 

embryonic development

• provide scaffold for 

migrating cells

• provide structural support

• provide progenitor cells

 

• neural progenitor cell during 

embryonic and post-natal 

development

•Generate progenitor 

populations in adult 

Term
Memorize slide 5
Definition
Term
What do gradients of signaling molecues result in?
Definition

- result in the formation of distinct progenitor domains within the neural tube

- especially the pMN domain which gives you almost of the neurons and is the primary spot for glia development 

- this shows that from a single domain, you get all of the different glial cells. 

 

Term
What do the glial cells have in similarity/ differences (or be able to be distinguished from neurons) with neurons?
Definition

• The same precursor cells 

as neurons

• The same progenitor 

domains as neurons

• Differentiated from 

neurons by:

• transcriptome

• form

• func

Term
How do you determine where cells come from?
Definition

Where do these cells come from? 

one way is "fate" mapping - label or tag a progenitor cell and that tag is maintained in all the daughter cells. 

 

take a retrovirus, if cell gets infected, all its daughter cells would have the virus. 

Term
Describe the maturation of neurons and glia in the mouse CNS.
Definition

The top line shows that a tissue explant and everything is all together. They will produce stem cells at the right time. but if you take them and remove them what they will turn out to be is just the ones that hey should be producing at THAT time. 

 

Although these functional cells mature around the time shown above, the progenitors are specified and formed prior to this time. 

Term
What are Radial Glia and how are they organized in the developing CNS?
Definition

• Appear early in development

• Early progenitors for all CNS cells

• RG-like cells maintained in adult

• Provide scaffold for developing CNS 

 

RG-like cells are maintained in the adult

• Tanycytes  (Hypothalamus)

• Bergmann glia (Cerebellum)

• Müller glia (optic nerve

 

THe 'inside-out " organization of the developing cortex is directed by radial glia. 

 

--> they are more that just a scaffold. Radial glia can become Neurons, Astrocytes, Oligodendrocytes, and 

Ependymal Cells …as well as their precursors!

radial glia also produce other cells. 

they start to form a typical radial glia morphology  and extend long surface to cortex. they spit a neron off. Once radial cells finish scaffolding, they can let go of the bottom or they let go of both sides and become oligodendrocytes OR they becomes ependymal cells  that line the cerebral spinal fluid etc. 

Once in adult, they becoe subventricular zone astrocytes (type B cells) 

 

** can build nervous system without them.  

 

Term
What are astrocytes?
Definition

• Provide structural and metabolic 

support to CNS

•  Blood Brain Barrier (BBB)

•  Control vasculature

•  Modulate synaptic transmission

•  Neurotransmitter uptake/release

• 3D positional information??

Term
What is the Blood Brain Barrier?
Definition

• Maintains the integrity of the CNS as separate from the PNS and other tissues

• Regulates which cells/molecules can enter the CNS compartment and when 

• Formed initially by endothelial cells and Radial Glia

• Maintained by Astrocytes throughout life

• BBB breakdown after trauma or autoimmune/neurodegenerative pathology is a 

major sequalae in CNS injury 

 

pericytes are epithelial cells and they are not glia because they are at wrong side of BBB. 

 

purple line is the astrocyte basement membrane. basement membrain are overlapping and allows lots of communication between epithelia and astrocytes and allows transport. 

 

BBB is everywhere. Around every blood vessel of the brain, it is surrounded by astrocytes. 

 

--> they also modulate synapses beyond metabolic support. THey are involved in: 

formation/pruning of developmental synapses

adult plasticity

 

--> astrocyte precursors also create a scaffold for the developing nervous system. 

Astrocyte precursors and their progeny appear restricted to specific 

domains. Is positional information encoded therein? 

Term
What is Microglia?
Definition

• Macrophages of the CNS

• Descended from monocytes (Mesoderm)

• Distributed relatively evenly throughout CNS  

 CNS Immune 

surveillance 

• Regulate 

neuroinflammation

• Clearing debris

• Provide trophic 

support (BDNF

• Microglia promote learning-induced synapse formation 

• Effects on neurons act through BDNF signalling

• Promote synapse formation as well as pruning 

Term
What is the advantage of Myelination?
Definition

• Myelin: a compact, multi-lammelar sheath of insulating, 

lipid-rich plasma membrane provided by glia

• Myelin allows saltatory conduction of APs along axons

• Necessary with space constraints of skeleton

• Metabolic and functional support for neurons

it packs down multilayer of lipid rich around axon and insulates it so that action potential can't travel that part of the axon so that its forced to jump on the node of ranvier. 

- so you can get neuron to be very small but still travel very far. 

- this is done by oligodendrocytes and schwann cells 

 

- PNS have a basal lamina which is providing protection from extracel to center of neuron. 

Term
Wat are Schwann cells?
Definition

• Myelinating glia of the PNS

• Myelinate one internode per cell

• Descended from Neural crest cells

• Can also be produced by PDGFRα+ 

precursors (OPCs) after injury

• Can de-differentiate into a SC 

precursor after injury!

• Therapeutic potential as a cell 

transplant for CNS repair

• Can be derived from skin-derived 

precursor cells (SKP-SCs)

• Provide a permissive environment 

for regenerating axons 

Term
What are Oligodendrocytes?
Definition

• Myelinating glia of the CNS

• Descended from Oligodendrocyte Progenitor Cells (OPCs)

• Committed once differentiated (myelinate or apoptose…) 

• Myelinate multiple, non-consecutive internodes (up to 50!)

• Regulate metabolism and nutrient transport in axons

• Membranes can depolarize to modulate transmission speeds 

in neural circuits

• Individual OLs complete 

myelination within ~5hrs of 

becoming myelogenic

• Oligos that fail to myelinate in 

this time window will apoptose

• Once differentiated, OLs must 

myelinate…OR DIE!

Czopka et al 2013 Developmental Cell 25:599-609 

• Oligodendrocytes 

are generated in 

adult life

• Aged cells are 

replaced by freshly 

generated ones 

throughout life

• Old-born OLs have 

different dynamics

• More internodes

• Shorter internodes

• Myelin is dynamic!

• Role in plasticity?

 

Term
What is the liquid croissant model?
Definition
have to spin the axon. these are fluid plasma membrane. the domain ols attached to are spinning. ols membrain are staying put and spitting out membrane but it is the axon that is spinnning.
Term
What is oligodendrodia?
Definition

a broad term including all the components of the oligodendrocytes. 

- ventral at p3 occurs first than moves upwards. They all come from the pMN domain

 

 OPCs emerge first ventrally and then dorsally , and primarily 

myelinate the spinal cord and brain, respectively.

Term
What is the pMN domain?
Definition

 Diffusible gradients 

create distinct 

domains in the 

developing neural tube

 Motor neurons (MNs) 

and OPCs are both 

produced in the pMN

domain at E8.5 and 

E12, respectively

 The pMN  domain is 

defined by Olig2 

expression

-diffusible gradients create the distinct domains 

- * on left* have a series of transcription factors. looking at this figure how to define pMN domain? identify it? 

- the pMN domain is defined by Olig2 expression. 

Term
The borders of the pMN domain are defined by what?
Definition

defined by cross-repression 

• Dbx2 vs. Nkx6.1 (dorsal)

• Pax6 vs. Nkx2.2 (ventral)  

Cross-repression: Two factors that each 

suppress the function of the other! 

Term
Know the timeline of the timeline of pMN development
Definition
Term
What is the Notch signalling in the pMN?
Definition

• Proneural gene 

expression in a subset 

of pMN cells leads to 

Delta expression 

(prospective 

motoneurons)

• This Delta expression 

activates Notch 

signaling in nearby 

cells  prevents 

neuronal 

differentiation

 

Zebrafish  spinal cord

Notch1a = constitutively active 

Notch 

Hu: neurons

Olig2: OPCs 

Term
What is the role of Nkx2.2 in the pMN?
Definition

Early on, progenitor domains are 

separated via Nkx2.2 repression of 

Olig1/2 expression

 

During OPC migration 

fom the pMN domain 

into the mantle zone, 

Nkx2.2-Olig1/2 

repression is lost; coexpression is required 

for appropriate 

maturation

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