Axonal growth, synaptogenesis and tropism Lec 3 Flashcards
Polarization
First step in neuronal identity
one process becomes axon
-with growth cone
Axonal growth cone structure and fxn
Explores EC env
determines direction of growth
Guides extension of axon
Lamellapodium
actin filaments and mircrotubules
Filopodia
Extends out of lamellapodium
actin filaments
form and disappear rapidly
Globular actin (G-actin)
part of growth cone cytoskeleton
can be incorporated into F-actin
Respond to environmental cues
Growth cone turning
Binding of F-actin -recruits proteins attractive cues -assembly increased retrograde slowed turns to attractive cue (repulsion opposite)
Microtubules
Stability and strength
Discrete regions of cytoskeleton
F-actin- lamellipodium
Tyrosinated microtubules- lamellipodium
acetylated microtubules- axons only
Guidance molecules- nondiffusible
contact attraction
contact repulsion
Guidance molecules- diffusible
Chemoattraction
chemorepulsion
Attractive interactions
Actin polymerization
Repellent interactions
actin depolymerization
PNS molecules
Laminins collagens fibronectin - bind integrins - leads to axon growth and elongation
CNS molecules
Hyaluronan
proteoglycans
glycoproteins
- repulsive to axonal growth and inhibit cell movement
Cell adhesion molecules CAMs
Non-diffusible
Ligands and receptors on surface of axons/growth cones
Ca independent
Induces interation with cytoplasmic kinases in growth cone
attraction
Cadherins
Non-diffusible
Ligands and receptors on surface of axons/growth cones
Ca dependent
triggers intercellular signaling pathways that lead to actin binding and organization
Attraction
Semaphorins
Non-diffusible
Cell surface
Repellent
Growth cone collapse and inhibition of axon extension
Ephrins
Non-diffusible cell surface like CAMS Ephrin A- GPI linked Ephrin B- single pass transmembrane protein Repellent- collapse growth cones
Netrins
Diffusible
Midline of embryo
Attractive and repellent- depends on receptor
DCC= attractive
UNC5= repellent
Key role in commissural axonal crossing in developing spinal cord
Slits (robo)
Diffusible proteins
repellent
Netrins and slits in commissural axons
DCC expressed- attracts to midline
- produces high level of netrin
Slits (robo) upregulated
- inhibits DCC signaling
Synaptogenesis NMJ
Motor axon- myotube differentiation occurs by argin - produces MuSK- clustering of AchR and rapsyn ECM formed -make basal lamina -stabilizes synaptic structure
Synaptic specificity
T1-eye
T4-ear
both use same sympathetic pathway
differential innervation occurs at level of synapse formation
CNS synaptogenesis
Neuroxin and Neuroligin
Neuroxin
Presynaptic
- cytoskeletal elements
- Synaptic vesicles
- Ca channels
Neuroligin
Postsynaptic
-NT receptors
PNS synaptogenesis
Neurons dependent on targets for survival and differentiation
Neurotrophic factors
-Skeletal muscle fibers and some parasym neurons innervated by multiple neurons- synaptic input are gradually eliminated until only one remains
Neurotrophic factors
Neurons compete for limited supply
Neurotrophin family
Nerve growth factors
-acts on specific popns of peripheral neurons
different neurons respond differently to NGF
Neurotrophin family fxn
Survival
Formation/maintenance
synapses formation
Neurotrophin receptors
Trk
P75
Trk receptor
High affinity for processed (cleaved) neurotrophins
P75 receptor
High affinity for unprocessed (uncleaved) neurotrophins
-can be activated by all neurotrophins
Neurotrophin signaling
Specific cascade activated determine cellular response
Neurotrophin signaling interactions depend on and determine what
Depend on
- neurotrophins secreted by target cells
- neurotrophin receptors on neuron
- intracellular signaling cascades present in neuron
Determine
- number of neurons
- shape
- pattern of connections
