Lecture 3: Axonal Growth, Synaptogenesis, and Tropism Flashcards
What structure defines the polarity of the neuron? What is at the tip of this structure?
Axon
Growth cone
What is the growth cone and what does it do?
- key decision-making structure in axon pathfinding during neuronal development
- explores extracellular env, determines direction of growth, guides extension of axon
What two morphological characteristics are present in growth cones?
lamellapodium
filopodia
How is a lamellapodium characterized?
- fan-shaped, tip of axon
- contains actin filaments and microtubules
How are filopodia characterized?
fine processes extending out from lamellapodia
- contain actin filaments
- form and disappear rapidly
What molecule is in both lamellapodium and filapodia?
F-actin
Where are tyrosinated microtubules found?
enriched lamellipodia
Where are acetylated microtubules found?
axons
What process is key to growth cone turning, and regulates retrograde flow?
F-actin binding proteins to F-actin
How do microtubules affect the core cytoskeleton in the axon?
stability, strength
What are the four types of axon guidance signals? Are the diffusible or non-diffusible?
- contact attraction - non-diffusible, short range
- contact repulsion - non-diffusible, short range
- chemoattraction - diffusible, long range
- chemorepulsion - diffusible, long range
Where do axon guidance molecules bind?
receptors on growth cones
What are non-diffusible attractive guidance molecules for growth cones in the PNS? To what do they bind?
- laminins, collagens, fibronectin
- bind growth cone receptors = integrins
What are examples of non-diffusible guidance molecules in the CNS? Are these attractive or repulsive?
-aggrecan, hyaluronan, tenascin
repulsive –> inhibit cell movement/axon growth
Describe Cell Adhesion Molecules (CAMs)
- located: surfaces (growing axons, growth cones, surrounding cells/targets)
- non-diffusible
- attractive (homophilic binding)
- calcium independent
- facsiculation (bundling) of axons
Describe Cadherins
- located: surfaces (growing axons, growth cones, surrounding cells/targets)
- non-diffusible
- attractive (homophilic binding)
- calcium dependent
- actin binding and organization
Describe Semaphorins
- secreted or anchored to cell surface
- non-diffusible
- mostly repellant
- growth cone collapse, inhibition of axon extension
What are semaphorin receptors on growth cones? How do the surface and secreted forms bind to these receptors?
- plexins
- surface/anchored forms bind directly to plexins
- secreted forms bind neurophilins, which then bind to plexins
Describe ephrins
- on cells surface
- non-diffusible
- repellant
- bi-directional signalling molecules
How does ephrin A differ from ephrin B?
Ephrin A = GPI-linked to cell surace
Ephrin B = single-pass transmembrane proteins
What does it mean that ephrins are bi-directional signaling molecules?
both growth-cone bearing cell and target cell will respond
What signaling molecules guide projections from the retina to the optic tectum?
ephs and ephrins
Axons in the developing temporal retina make connections with what portion of the tectum?
anterior tectum
Axons in the developing nasal retina make connections with which portion of the tectum?
posterior tectum
In what fashion are ephrins expressed in the optic tectum?
anterior-to-posterior gradient
Describe how ephrins guide the correct projections from the temporal and nasal retina to the optic tectum
- Axons from temporal retina have Eph receptor –> repulsed by ephrin in posterior tectum –> bind anterior tectum
- Axons from nasal retina lack Eph receptor = blind to ephrin –> can bind posterior tectum
Are netrins diffusible? What are receptors for attractive vs repulsive netrins?
- Diffusible
- Attractive receptors = DCC
- Repulsive receptors = UNC5
Are slits diffusible? Are the attractive or repellant? What are their receptors?
- Diffusible
- Repellant
- growth cone receptors = Robo family
Netrins play a key role in _____ crossing in the developing ______
comissural axon
spinal cord
In comissural axon crossing: Comissural axons express 1____ and are originally attracted to the 2____, which produces high levels of netrin. As they cross the midline, they upregulate 3____, which keeps them from 4_____ because of the high levels of 5_____ at the midline.
- DCC
- midline
- Robo
- recrossing
- slit
If two different axons use the same guidance cues, how is synaptic specificity achieved?
differential innervation of ganglionic neurons
How do incoming axons preferentially form synapses on the correct targets?
pre- and postsynaptic neurons have higher affinity for each other
Synaptogenesis at the neuromuscular junction:
Motor axon makes contact with 1____. Subsequent differentiation of the nerve terminal and myotube is induced by 2____, which activates 3____, causing clustering and increased local exp of 4_____ through the adaptor molecule 5______.
- myotube
- agrin
- Muscle activated kinase
- acetylcholine receptor
- rapsyn rapsyn
In synaptogenesis at the neuromuscular junction, what do the nerve terminal and myotube differentiate into?
nerve terminal –> motor terminal
myotube –> postsynaptic apparatus
In synaptogenesis at the neuromuscular junction, both the motor nerve and the muscle make ECM components to form a _____, which stabilizes the synaptic structure
basal lamina
In synaptogenesis in the CNS, ____ helps localize cytoskeletal elements, synaptic vesicles, active zone proteins, and voltage gated Ca2+ channels to the _______
Neurexin
presynaptic membrane
In synaptogenesis in the CNS, ____ recruits neurotransmitter receptors and other postsynaptic proteins to the ______
neuroligin
postsynaptic membrane
How do target cells support survival and differentiation of neurons after synaptogenesis?
secrete neurotrophic factors in limited amounts
- neurons compete
- target cells help determine the # of cells which innervate them
Nerve growth factor (NGF) is part of the _______ family
neurotrophin
What are 4 pieces of evidence for the trophic function of NGF?
- absence of NGF –> neuronal death
- Increased NGF –> survival of excess neurons
- presence and production of NGF in target cells
- presence of NGF receptors in innervating nerve terminals
What are three functions of neurotrophins?
1 survival of subset of neurons
- # target cells contacted
- # synapses formed
Trk receptors and p75 receptor are _____ receptors
neurotrophin
What are Trk receptors? What do they bind? What form of this molecule do they bind preferentially?
- receptor tyrosine kinases
- bind processed (cleaved) neurotrophins only
What is p75 receptor activated by? For what molecule does it have a high affinity?
- activated by all neurotrophins
- high affinity for unprocessed neurotrophins
What are the three cellular cascades which can occur from neurotrophin signaling?
- cell survival or death
- growth or differentiation
- stabilization or elimination of synapses - activity-dependent
