Unit 3 Flashcards
Pioneer axon
The first axons that emerge during development
Guidepost cells
Provide short-range attractive cues for emerging axons
Four types of molecular cues
Contact Adhesion, Contact Repulsion, Long-range Attraction, Long-range Repulsion
Contact Adhesion Example
increased polymerization in growth cone due to receptor-ligand interactions
Contact Repulsion Example
Increased DEpolymerization in the growth cone due to receptor-ligand interactions
Long-range Attraction Example
Diffusible chemoattractants
Longe-range Repulsion Example
Diffusible negative cues
Filopodia
Thin actin filament protrusions from the growth cone; probing the environment for cues
Lamellipodia
Dense sheets of actin; provide the motile force along the leading edge of the growth cone
Is the growth cone autonomous?
Yes; severing the axon from the cell soma doesn’t stop the axon from making decisions (in the short time it lives w/o resources)
P Zone
The peripheral zone of the growth cone; forms the lamellipodia, the filopodia and the veils between the filopodia
C Zone
The central zone of the growth cone; microtubules from the axon end here
Axon navigation is ___ not ___
extrinsic, not intrinsic; they rely on cues from the environment
Rotation of rhombomere 4 by Mauthner resulted in axons that usually emerge and travel caudally to
emerge rostrally, following the cues of the transplanted tissue, but once they reached the original tissue, they reoriented and traveled caudally
F actin
Filamentous actin; bundles of actin that form the filopodia
G actin
monomers of actin assembled at the tips of the filopodia
Role of myosin in axon growth
Myosin provides the force pulling the filopodia rearward (toward the axon since filopodia work like tank treads) aka it drives the retrograde flow of actin
Microtubules and tubulin in the growth cone
Pools of tubulin are concentrated in the growth cone; tubulin is polymerized into microtubules which run parallel through the axon
Retrograde
Moving backwards (towards the cell soma)
Anterograde
Moving forward (toward the growth cone)
Microtubule-associated proteins are
proteins that help regulate the growth process in the growth cone. Some stabilize microtubules, some crosslink actin and microtubules; overall, they are responsible for the assembly and disassembly of microtubule and actin filaments.
Effect of cytoskeletal drugs on growth cone
Adding actin-depolymerizing cytochalasin or microtubule-destabilizing nocodazole causes the axon growth cone to collapse and turn away. Adding the microtubule-stabilizing taxol causes the axon to turn towards the drug.
Cytochalasin, nocodazole, taxol
Actin depolymerizing, microtubule destabilizing, and microtubule stabilizing, respectively.
Dendrite formation is
more complicated than axon formation since each neuron has multiple dendrites. Actin is less uniformly oriented in dendrites, MAPs are differentially associated, BMPs selectively induce the formation of dendrites.
What is integrin?
a receptor for many different ECM proteins. it is made up of two subunits with different variations for each. the type of integrin receptor an axon has determines which molecule it will be sensitive to (eg. laminin)
Cell adhesion molecules (CAMS) can be either ___ or ___ but most are ___
heterophilic (bind to different molecules) or homophilic (bind to similar molecules); most are homophilic
chemotaxis
movement of a motile cell in correspondence with a gradient of a particular substance
Examples of CAMs
IgG family and calcium-dependent cadherins
In terms of supporting axon growth, fibronectin is preferred by the ___, and laminin is preferred by ___
Fibronectin is preferred by the PNS and laminin is preferred by the CNS
What is the labeled pathway hypothesis?
As pioneer axons grow, they express specific CAMs on their cell surfaces which creates a labeled path for the subsequent growth cones.»_space; “Guidance along previously pioneered tracts by selective adhesion.”
Role of Semaphorins in axon development
Semaphorins signals are arranged to repel axons that contain the Sema receptor
Role of Slit
Responsible for the guidance of olfactory tract axons away from the septum
Ephrin A is a membrane-bound receptor that ___ axons
repulses; Adding Ephrin A causes the growth cone to collapse;
Ephrin ligands and Eph receptors first regulate ___ then they regulate ___
tissue patterning then axon pathfinding
Which category of molecular cues does Epherin fall into?
Contact Repulsion
Which category of molecular cues do Semaphorins fall into?
Lone-range repulsion
Results of a semaphorin knockout in a mouse model
No repulsion in PNS, too many axons grow in the head and limb buds of the developing mouse
What is an open-book assay?
A method of observing axon growth by splitting the neural tube down the middle and laying it flat.
What are commissural neurons?
Neurons that travel across the midline of an organism; aka contralateral axons
When does interstitial growth occur in neurons?
When the embryo is growing in size
Cadherins allow neurons to ___
stick to each other and follow the same path
Which molecular gradients help dorsal root ganglion neurons to stay dorsal and avoid ventral tissue?
Shh (high ventral) and Bmp (high dorsal)
Semaphorins are almost always
repulsive to axons
Nerve Growth Factor (NGF) is an example of a ____
diffusible chemoattractant
Axon growth response to the removal of destination (tectum in Xenopus embryo)?
The axons still grow toward their final destination even when it is not there. This indicates that local cues are used and not a long-range signal from the axon destination.
Netrin is a long-range ___ that attracts ____ to ___
long-range chemoattractant that attracts interneurons to the floorplate of the neural tube
A high anterior/low posterior Wnt gradient is responsible for ___. It acts through the ___ receptor
anterior migration of axons; it acts through the fz3 (frizzled 3) receptor
Shh acts through the ___ receptor and is ___ then ___ to commissural neurons once they pass through the midline
Shh acts through the Boc receptor and is attractive to commissural neurons before and repulsive to them after they pass through the midline.
Intracellular signaling works through ___ and ___
kinase receptors and phosphatases
How do retinal ganglion cell (RGC) axons follow the pioneer axon to the optical fissure?
They use homophilic CAMs that expresses attractant Shh
What are the 5 steps for RGCs to reach the optic tectum?
- enter the optic nerve, attracted to Shh and Netrin
- at the optic chiasm slit and Shh are repulsive to axons
- dorsal/medial RGCs that are insensitive to EphB are contralateral, while those sensitive to EphB are ipsilateral bc they are repulsed from the midline
- Repulsive signal from Semaphorin 3a guides axons to the rectum
- Drop if FGF indicates that axons have reached their target (FGF is usually attractive to neurons)
What is defasciculation?
Axons break away from the axon bundle and branch out to create synapses.
What is the strategy for an axon to enter its target region?
A drop in an attractive signal causes the axon to pause
How is axon branching encouraged?
A repulsive signal prevents the axon from leaving its target site. This pauses the axon and the pause destabilizes the cytoskeleton, inducing branching.
What is the Sperry experiment?
cut the optic nerve in amphibians and rotate the eye 180 degrees. If chemical gradients determined the map, then visual perception will be flipped. If through experience only, then visual perception will not be flipped. (Result? chemical gradients, so rotated eye retained its usual identity causing flipped vision)
What keeps a neuron from dying during development?
Trophic factors, paracrine (nearby cell) signaling, vasculature support (blood vessels), neuron support
Apoptosis rate is highest in neurons when
their target tissue is developing
Removing a limb bud during neuron development leads to ____ because ___
Removing a limb bud during neuron development leads to increased neuron cell death because there are less signals preventing them from dying (and less target tissue to innervate)
Adding a limb bud during neuron development leads to ___ because ___
Adding a limb bud leads to decreased cell death because there is more tissue for neurons to innervate and more signals keeping neurons alive
What is the neurotrophic hypothesis?
target tissues supply trophic factors that drive competition between neurons for survival
The first neurotrophic factor identified was ___
Nerve Growth Factor (NGF)
The anti-apoptotic pathway:
MAPK and PI3K pathways inhibit apoptosis by phosphorylating CREB which turns on anti-apoptotic genes; these pathways also degrade phosphorylated c-Jun
The pro-apoptotic pathway:
Cdk and JNK pathways encourage apoptosis by phosphorylating c-Jun-1 which activates pro-apoptotic genes
The three rules of synaptogenesis:
- proteins involves in synapse formation are present before the synapse forms
- Synaptogenesis involves intracellular signaling cascades at the time of neuron contact
- Synapses take time to mature before they are fully functional
As the synapses mature, nerves respond more ___ and ___
more quickly and accurately
Young neurons switch from ___ channels to ___
They switch from slower calcium channels to faster sodium and potassium channels
Characteristics of a mature synapse:
- presynaptic vesicles accumulated at the presynaptic membrane
- thick ECM between pre and postsynaptic membranes
- postsynaptic membrane is thickened with postsynaptic proteins»_space; aka the postsynaptic density
Where do synapses form?
For the CNS: excitatory (glutamatergic) synapses form on the dendritic spines; inhibitory (GABAnergic) synapses form on the cell soma (more direct);
For the muscle: in the middle of the myofiber
