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
|
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
|
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
|
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
|
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
|
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
|
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 |
|
|