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What is the growth cone responsible for?
Sensing environmental signals to guide the neuron
What does the growth cone use to probe its surroundings?
Filopodia
Lamellipodia
What are the different long-range cues?
Chemoattraction
Chemorepulsion
What is an example of a chemoattractant?
Netrin
What is an example of an chemorepelant?
Semaphorins
What are the different guidance mechanisms?
Long-range cues
Short-range (contact-dependent) cues
What are the different short-range cues?
Contact attraction
Contact repulsion
What is an example of a contact attractant?
Cadherin
What is an example of a contact repellent?
Eph ligands
What are the different conserved molecular families of directional guidance cues?
Netrins
Semaphorins
Slits
Ephrins
What are the different signal transduction and regulation cues for physical movement?
Rho Family Small GTPases
Differential interpretation
Gradients
How do the Rho Family Small GTPases mediate guidance?
They interact with the various signaling pathways to alter the cytoskeleton and cell morphology
What is differential interpretation?
The same receptor-ligand interaction can result in different outcomes depending on the cell type or the specific receptor complexes formed
What are the key genes that came from studies of unc mutants in C. elegans?
UNC-6
UNC-5
UNC-40
What genes are receptors for netrin?
UNC-5
UNC-40
What does the inhibition of UNC-6 result in?
Both neurons failing to migrate
What does the inhibition of UNC-5 result in?
The motor neuron failing to migrate
What does the inhibition of UNC-40 result in?
The sensory neuron failing to migrate
What does the mutation of the unc genes affect?
Axonogenesis and outgrowth
The ability of axons to form fascicles (bundles)
Directionality of outgrowth
What is the netrin gradient in the nerve cord?
Dorsal (none) to Ventral (high)
What is netrin similar to?
Lamin
Describe commissure neurons
Connect to the other side of the body
Always cross the midline
What is the purpose of both netrins and Slits?
Neuronal and mesodermal cell migrations
What is the purpose of semaphorin?
Neuronal cell migrations
Bone and heart morphogenesis
What is the purpose of ephrins?
Neuronal and neural crest cell migrations
Angiogenesis
What do special nerves go to?
Cadherins
What is not attracted by netrin?
Dorsal trochlear axons
What happens when only UNC-40 is expressed?
Neurons are attracted to Netrin
What happens when both UNC-5 and UNC-40 are expressed?
Neurons have a repulsive signal
What is the function of Slit?
Acts as a repellent to block neurons from crossing or to ensure they keep moving once they have crossed
What happens during the midline crossing?
Axons use Netrin as a chemoattractant and Slit (using Robo receptors) as a repellent to block neurons from crossing or to ensure they keep moving once they have crossed
What happens in Robo mutants?
Neurons try to cross but fail to leave the midline, staying stuck there
In amphibians, what happens if the optic nerve is severed and the eye is rotated 180 degrees?
The regenerating axons, instead of adapting to the new orientation, they re-establish their original connections, leading to inverted visual behavior where the animal attacks in the opposite direction of its target
How is the choice of target by retinal axons mediated?
By repulsion
What is the relationship between high concentrations of EphA3 receptors on temporal axons and Ephrin A2 ligands in the posterior tectum?
A repellent one, so when they interact, the axon’s growth cone collapses and it is forced to find its correct target somewhere else
What is the function of Sonic the Hedgehog (Shh) as a morphogen?
Ventral inducer (secreted by the notochord)
Establishes neural tube polarity
Stimulates the formation of neural folds
Induces myoD expression in the paraxial mesoderm (future somites)
What cells are nicknames the “fourth germ layer”?
Neural crest cells
Where do neural crest cells originate from?
Originate from the apical part of the developing neural tube
How is the fate of neural crest cells determined?
Determined by their position along the embryo
What does receptor heterodimerization entail?
The same guidance cue can induce opposite behaviors depending on the receptors present
What is the physical process for the formation of the neural crest
Neural fold formation (stimulated by Shh signaling)
Invagination (folds move toward each other)
Fusion (forms neural tube)
Delamination and migration
What are the different derivatives of the “fourth germ layer”?
Melanocytes
Glial Cells
Nervous system components (different neurons)
Endocrine cells
Skeletal structures (cartilage)