Glia In The Developing Nervous System Flashcards
Glia types
Radial glia
Microglia
Ependymal cells
Astrocytes
Oligodendrocytes and OPCs
Roles of radial glia
-developmentally transient (not in mature brain)
-neurogenesis
-guide migration
-connectivity
-in cortical development/retinal muller glia/cerebella’s Bergman glia
Radial glia neurogenesis
Polarised neuroepithelium undergoes interkinetic nuclear migration and divides symmetrically
Loss of ZO1+ tight junctions and decreased FGF10 cause neuroepithelium to form ventricular radial glia in VZ
Radial glia division
Early RG expand symmetrically to expand pool
RG undergo asymmetric division to produce IP (delaminate to SVZ) and self renew to from neurons
how do radial glia direct neurogenesis
neurons migrate to the cortical plate via RG basal processes as a scaffold
what is a RG detachment cue
sparc like 1 SC1 in cortical plate
what type of migration do excitatory neurons undergo
radial migration
what type of migration do inhibitory interneurons undergo
tangential migration
how to RG inhibit axogenesis
RG interact via N-cadherin to drive RhoA
how to RG promote axonogenesis
RG use Rac1 (trailing process)
how to RG influence connectivity - experimental procedure
(Yu et al., 2009)
in utero retrovirus (selectively produces dividing cells)
sparsely label clonally related sister cells
simultaneously record sister cells (red and green) and unlabelled neighbouring cells (red only)
greater connectivity probability in sister cells
microglia roles
main CNS resident macrophage (1st line defence)
surveillence and engulfment of pathogens
professional sensors at chemical interference of brain and body
adopt distinct states depending on context
how is microglia formed
from yolk sac (YS) erythromyeloid progenitors (EMP)
migrate to brain in blood and arrive before BBB closes
EMPs differentiate and self renew to microglia
what does microglia survival and differentiation require
CSF-1R (receptor) activation by IL-34 (from neurons and or CSF1 (astrocytes/OL) and TGFbeta signalling from astrocytes
which cells do microglia remove
microglia engulf cortical neuronal precursor
microglia promote cell death - purkinje cells undergo apoptosis (marin-teva et al., 2004) CaBP stains for purkinje cells (main projection cells in cerebellum)
how do microglia prune synapses
activity dependent segregation in mouse dLGN in thalamus - sharp C and I border (Guido, 2018)
Gabaergic synapses pruned by microglia via phagocytosis requires CR3-C3 signalling
how do microglia promote synaptic strength in the olfactory system
CSF1R inhibitor (PLX5622) then GCamp injection - smaller responses to olfactory stimulation and less excitation
no effect of microglia depletion if done after abGC maturation
how do microglia cause synaptic remodelling
clearance of dense ECM
how to microglia restore ocular dominance plasticity (Venturino et al., 2021)
perineuronal net formed around PV+ inhibitory interneurons and ends critical period
microglia can breakdown perineuronal net via ketamine anaesthesia/60Hz light entrainment
restores ocular dominance plasticity
what do ependymal cells consist of
ciliated simple cuboidal epithelium
ependymal cells roles
regulates blood-CSF interactions at choroid plexus
line ventricles for CSF-brain interactions
CSF dynamics via beating cilia in ventricular space
ependymal cells development
derived from RG (E16-18)
form cilia and adhesion molecules for barrier formation and joining
ependymal cells position into rossette structures surrounding CSF, contacting tips of adult NSC
how do ependymal cells direct neuronal migration
neuroblasts in adult SVZ follow RMS CSF flow via beating cilia
orpk mutants - few/short/irregular cilia. disordered migration of neuroblasts
CSF deposits slit2 gradient caudally, slit2 repels neuroblasts
astrocyte roles
maintain BBB via end feet
regulate and support neurotransmission
metabolic support
SC pool
wave 1 (prenatal) of astrocyte development
late development (after microglia)
cortical SVZ RG form neurons (asymmetrical division)
RGs form translocating RGs E16.5 (requires EGFR and cytokine expression)
tRG use radial migration to form astrocyte progenitor cells
APCs undergo symmetrical division to produce astrocytes
wave 2 (postnatal) of astrocyte development
cortical SVZ RG produce IP (EGFR and Ascl1 upregulation)
basal multipotent IPCs (bMIPCs) proliferate rapidly
bMIPCs express both astrocytes (Glast) and OL (olig1/2) markers
OPCs - downregulate EGFR
APCs - maintain EGFR
astrocytes and neuronal migration
thalamic astrocytes produce downstream components of Shh
deletion of shh
decreases FGF15 mRNA
decreases % of interneurons recruited into visual thalamus (less GAD1 (GABA production))
how do astrocytes cause synaptogenesis
B cells (astrocyte SC contact CSF)
C cells
A cells
TSP KO in retinal ganglion cells
reduces synaptic terminals (astrocytes)
B1 astrocyte stem cells
produced E13.5-15.5 remain quiescent until reactivated postnatally
astrocytes and ependymal cells have the same lineage
GEMININ = more astrocytes
GEMC1 = more ependymal cells
oligodendrocyte roles
insulation - increased membrane resistance , fast saltatory conduction at nodes of ranvier
metabolic - supply mitochondria with substrates for oxidative phosphorylation
schwann cells vs OLs
schwann cells myelinate just one axon
OLs myelinate many axons
development
where do OLs arise from
bMIPCs in cortex to form OPCs
OPCs populate both white and grey matter
name OPC markers
OLIG2
NG2
PDGFRa+
NKX2.2
name myelinating OL markers
OLIG2
GalC
CNPase
MBP
MAG
MDG
how do myelin sheaths form
neurofascin clusters accumulate prior to myelination
neurofascin located at the nodes of ranvier
role of neurofascin
sets myelin position/cell adhesion molecule
learning dependent myelin dynamics
Bacmeister et al., 2022
adult mice trained on forelimb task
tdT = active cells in L2/3 neurons dependent on c-fos expression
changes node length
where do OPCs prune synapses
thalamus only
OPCs internalise presynaptic structures
what maintains myelin
microglia
what occurs in human adult onset leukoencepalopathy
reduces microglia
age related demyelination
how do OPCs migrate
use blood vessels
OPCs receive inhibition from blood vessel niche to prevent OL formation
how do astrocytes prevent OPC perivascular migration
astrocyte endfoot placement
astrocytes produce semaphorins 3a and 6a - repel OPC from blood vessels to detach and myelinate
endothelium niche prevents OPC differentiation. OPC detach to allow differentiation
