Chapter 54 - Axon Growth and Guidance Flashcards
when do differences in axons vs. dendrites emerge?
-early in development
what is a growth cone? (2 functions)
- sensory transducer
2. molecular motor
what does differentiation of axons and dendrites establish?
-neuronal polarity
how is neuronal polarity established?
-differentiation of axons and dendrites
what is stage one of axon/dendrite differentiation?
-lamellipodia formation
what is stage 2 of axon/dendrite differentiation?
-neurite formation
what happens after neurite formation?
one neurite becomes an axon
what happens to the other neurites that do not become an axon?
-they become dendrites
what happens if an axon is removed in vitro?
an existing dendrite is converted into an axon
what does the promotion of axon suppress?
axon formation in neighboring dendrites
what seems to promote axon specification?
-destabilization of actin filaments
what is required for neuronal polarization?
SAD kinases
what is a SAD kinase?
- par family gene
- involved in polarity
what factors determine whether a process becomes an axon or dendrite in vivo?
-extracellular factors
what is a common ECM protein?
-laminin
what happens to neurons grown on laminin?
-acquire polarity
do axons like laminin? does the cell body + dendrites?
- yes, the axon stays on the entire line and never leaves
- cell body + dendrites don’t show preference to be on the laminin
what do semporaphins do?
-provide axon guidance and tell dendrites where to go
what do semphorins attract?
-growing dendrites
what is Sema 3a?
- secreted by cells near the surface
- attracts growing dendrites
what happens in a Sema 3a mutant mouse?
neuronal polarity is disrupted
what are the 5 stages of dendritic branching?
- initiation
- outgrowth
- branching
- spine formation
- stopping/pruning
what happens to the morphologies of neurons in a dissociated cell culture? what does this mean?
- the morphologies are preserved
- neurons must have intrinsic information about their shape
what does the pyramidal cell in the brain vs. in culture reveal?
-suggests intrinsic transcription factor programs play key role in determining dendritic arborization + complexity
how are dendrites patterned?
-by intrinsic and extrinsic factors
what is dendritic tiling in Drosophila?
-dendrites of neighboring neurons provide cues to ensure non-overlap + coverage of a particular field
what is the normal expression of neurons in a drosophila dscam?
- normally, dendrites of two different neurons express distinct dscam splice variants
- allowing them to cross + cover overlapping receptive fields
what happens when both neurons are forced to express the same dscam isoform?
- they avoid each other
- fail to cover total field
what controls tiling?
- self-recognition of dendritic branches by others of same cells
- drives repulsion
what are 3 main domains in a growth cone?
- filopodia (sense chemical signals)
- lamellipodia (membrane movement)
- central core (rich in organelles/mitochondria)
where is actin concentrated?
-in filopodia/lamellipodia
where are tubulin/microtubules concentrated?
-in central core
what are filopodia/lamellipodia made of?
-actin
what is the central core made of?
-tubulin/microtubules
where does the growth cone receive directional cues from?
the environment
what drives elongation?
the growth cone
how is the growth cone directional?
-integrates positive/negative signals that regulate the cytoskeleton to guide pathfinding
how are growth cones extended?
- adhesion drives actin filament nucleation
- membrane exocytosis -> drives movement
what are the 4 steps to growth cone extension?
- filopodium contacts an adhesive cue -> pulls growth cone forward
- actin filaments assemble at leading edge, disassemble at trailing edge
- actin polymerization -> filopodium forward
- force generated by retrograde flow -> filopdium forward
where do actin filaments assemble? where do they disassemble?
- assemble at leading edge of filopodia
- disassemble at trailing edge of filopodia
what do actin filaments interact with along the way?
-myosin
actin provides ____ while microtubules provide ____
actin -> direction
microtubules -> force
what is actin depleted space filled by?
-advance of microtubules from the central core
what is the actin depleted space filled with?
-filled by the advance of microtubules from central core
how does the growth cone advance?
-under control of cellular motors
what must happen for the creation of a new segment of the axonal shaft?
- individual microtubules condense -> form thick bundle
- cytoplasm collapses
what pushes filopodium forward?
actin polymerization
what guide axons to their targets?
-molecular cues
how is adhesion converted into directional cues in the growth cone?
-changes in level of intracellular reg. proteins determine whether same extrinsic cue attracts or repels the growth cone
what happens when PKA activity and intracellular cAMP levels are low?
-growth cone is repelled by Netrin
what happens when PKA is high?
-increased cAMP -> growth cones attracted to local Netrin sources
do chemical or mechanical cues guide axons to targets?
-chemical cues guide axons to target
what experiment demonstrated chemical cues?
-you can cut axons and they will grow back in frogs
what is the organization of the frog visual system?
- lens projects inverted visual image onto retina
- optic nerve transfers image with more inversion to optic tectum
in a frog, where do anterior and posterior neurons project?
anterior -> posterior tectum
posterior -> anterior tectum
what happened in the frog experiment?
- retinal axons were cut
- eye inverted 180 degrees
what was the result of the frog experiment?
-visual information + wiring the same
-behavior is opposite
(molecular not activity defined)
what are 6 major types of extracellular cues that guide growth cones?
- extracellular matrix adhesion
- adhesion to other neurons
- adhere to other “pioneer” axons
- soluble chemical signals induce attraction
- cell surface repellent cues
- soluble chemical cues -> repulsion
how do various molecular families control growth + guidance of developing axons?
- extracellular domains that interact with ligands
- modulate cytoskeleton to promote assembly or disassembly
what are examples of diverse molecular families that control growth/guidance of axons?
-immunoglobins, ephrins, laminins, semphorins
what are commissural neuron?
- convey sensory info from spinal cord to brain
- at ventral midline of the spinal cord across the floor plate
what happens to commisural neurons after crossing?
-axons turn abruptly toward the brain
_____ direct developing commissural axons to cross the midline
netrins
what do netrins do?
mediate chemo-attraction or repulsion
where do netrins attract spinal commissural axons?
to the floor plate
how has the expression/activity of netrins been conserved through evolution?
-netrin is secreted by ventral midline cells in worms, flies etc.
what do netrins interact with?
-netrins interact with receptors on cells/axons that migrate or extend along the dorsoventral axis
what factors pattern the midline?
-chemo-attractant and chemo-repellent factors
