Axon Guidance And Synapse Formation - 32 Flashcards
How are axons directed to the correct target?
The follow their GROWTH CONE
What is the growth cone?
It’s a dynamic and motile structure on the leading tips of axons that explore their environment, determine direction of growth, and direct growth of axon in that direction
What are the two major structures of the growth cone?
Filopodium and lamellapodium
What are Filopodium?
Fine processes that reach out to sense the environment.
What are lamellapodium
Sheet-like extensions on the growing tip of an axon. (Often stretch between filopodium)
What movement is associated with filopodium?
Form and retract
What movement is associated with lamellapodium?
Ruffling
How do filopodia form?
Globular actin (G-actin) is incorporated into filamentous actin (F-actin) at the leading edge of a filopodia
How does an axon extend toward a given direction?
Attractive signals induce filopodia, and microtubules organize in the direction of the induced growth cone.
T/F Attractive cues promote the production of both filopodia and lamellapodia
T. They make up the growth cone
T/F there are no microtubules and F-actin in lamellapodia.
F - there are microtubules and F-actin in lamellapodia, but they are less organized
What are the 4 types of axon guidance signals?
Contact mediated attraction : Contact mediated repulsion : Chemoattraction : Chemorepulsion
What is contact mediated attraction?
Involved in axon fasiculation (bundling) and pathfinding
What is contact mediated repulsion?
Involved in axon defasiculation (separation) and pathfinding
What is chemoattraction?
Growth of axons toward a source of diffusible attractive molecules
What is chemorepulsion?
The directing of axons away from a source of diffusible repulsive molecules
What are tropic molecules?
Molecules that GUIDE the growth of an axon (chemoattractive/chemorepulsive)
What are trophic molecules?
Molecules that support the SURVIVAL and GROWTH of a neuron
What was the first thing to be associated with axon guidance?
ECM CAMs
Extracellular Matrix Cell Adhesion Molecules
S1/S2 ECM CAMs are secreted. They diffuse great distances.
T/F
ECMCAMs do not diffuse. They form polymers and a stable lattice.
What are the receptors for ECMCAMs?
Integrins
ECMCAMs are critical for _____________________ in the _______________ Nervous System where axons track along _______________.
Axon pathfinding : peripheral : basal lamina
What kind of guidance are ECMCAMs involved in?
Contact-mediated attraction
What are CAMs?
Calcium Independent Cell Adhesion Molecules
What expresses CAMs?
Growth cones, growing axons, surrounding cells, targets
What is the ligand for CAMs?
Themselves! They’re “hemophilic” they are the ligand and receptor.
What are the 2 important CAMs?
NCAM and L1
What function do CAMs serve?
Fasciculation
T/F Integrins and CAMs have intrinsic enzymatic activity
F - they have no intrinsic enzymatic activity, but are a part of signaling cascades
What do you call Calcium DEPENDENT CAMs?
Cadherins
What is the ligand for Cadherins? What do they require for binding?
Themselves! Homophilic : they require calcium to bind their Extracellular Domain
What would cadherins be involved in?
Contact mediated attraction
What is an example of a Chemoattractive molecule and a Chemorepulsive molecule?
Netrin : Slit
What do netrins look like?
Laminin (ECM molecule)
What is the main receptor for netrins?
DCC (no known intrinsic enzymatic activity)
How does Slit work?
It stops axons from turning back to regions of netrin.
What is the receptor for Slit?
Robo
Where do commissural neurons originate?
Near the roofplate (induced by noggin to be sensory??)
What are commissural neurons?
Neurons that send their axons centrally and cross the midline to the contralateral side of the spinal cord
What makes commissural neurons (growth cone) grow toward the floorplate?
Netrins expressed by the floorplate
Why don’t commissural neurons stay in the floorplate once there?
They are made insensitive to netrins by SLIT and are forced across the midline
What causes commissural neurons to say on the contralateral side?
Semaphorins
What are semaphorins?
A chemorepulsive molecule that can be diffusible or membrane bound
What are the receptors for semaphorins?
Plexins and Neuropilins
What is the largest family of chemorepelants?
Semaphorins
What are Ephrins?
Membrane-associated or transmembrane attractive axon guidance molecules
What is the only axon guidance receptor with intrinsic enzymatic activity?
Eph is a receptor tyrosine kinase
What is the receptor for ephrins?
Eph
What kind of axon guidance are ephrins involved in?
Contact mediated attraction
What is unique about ephrin signaling?
It can be bi-directional
What is bidirectional signaling?
Ephrins bind Eph (RTK) that causes phosphorylation/cascade in that molecule. But TRANSMEMBRANE Ephrins can signal into their own cell once bound to Eph!
In frogs, where to axons of the anterior retina project? Posterior?
Posterior tectum : anterior tectum
What is unique about the CNS in amphibians?
The neurons can regrow!
Where is the gradient of ephrin highest in the tectum?
Posterior
What are the two regions of the retina?
Nasal and temporal
How do neurons from the nasal and temporal retina find their spot on the tectum?
Ephrins guide them.
Nasal retina express high levels of EphA4 which will then recognize low levels of Ephrin A5 (low levels in the anterior tectum). Temporal retina express low levels of EphA4, so will not recognize the low levels, but recognize the high levels of Ephrin A5 being expressed in the posterior tectum
What is the humans version of the tectum?
The superior colliculus
T/F Axons have preferred neurons they will form a synapse with.
T - but they are not exclusive for 1 particular cell
Are there restrictions on the cells an axon will form a synapse with?
Yes. For example, an axon will never form a synapse with a glial cell
What axon guidance molecules are involved in selective synapse formation?
Ephrins and Cadherins
How do cadherins help form synapses?
Gamma-protocadherins is a CAM that can form hundreds of possible molecules. They are homophilic, so axons with them will only form synapses with dendrites with the correct protocadherins
How does the neuromuscular junction form?
Growth cone approaches muscle fiber. If its the correct class of muscle, they will make a contact, and the synaptic terminal will begin to differentiate. At this time, a basal lamina forms in the cleft. Multiple axons converge at this spot, then all axons converge into 1 keeping their separate contacts.
What are the important signaling molecules in the NMJ.
Again, Ach, and Neuregulin
What do Agrin/Ach/Neuregulin do in general?
They induce formation of post-synaptic structures in the muscle.
What does Neuregulin do in the NMJ?
Induces the formation of new Ach receptors.
What does Agrin do in the NMJ?
Induces the clustering of Ach receptors.
What is the receptor for Agrin? Neuregulin?
Musk : neuregulin receptor
What does Ach do in the developing NMJ?
It induces synaptic activity
What is the process of excess axons being lost from NMJs?
Synaptic Elimination
How do the correct axons stay behind in synaptic elimination?
Axons that fire synchronously with the postsynaptic muscle are strengthened. Those that don’t are eliminated.
(Neurons that fire together, wire together)
