Lecture 5 - Growth and Guidance of Dendrites and Axons Flashcards
What is the growth cone?
a sensory transducer and molecular motor
What do neurons in culture establish?
an axon and many dendrites
What happens if an axon is removed from the cell body in vitro during development?
an existing dendrite is converted to an axon which suggests that promotion of an axon suppresses axon formation in neighboring dendrites - a key step in this process is the destabilization of actin filaments which seem to promote axon specification
What are required for neuronal polarization?
SAD kinases
-the axon marker is tau and the dendrite marker is Map2
If you have a SAD kinase mutant what happens?
-sad kinase mutant and the neuron has neurites which keep growing but do not differentiate for axons or dendrites so have mixed tau and map2; happens spontaneously soon as one process becomes the axon the other ones cannot
In vivo what determines whether a process becomes an axon or dendrite?
extracellular factors - once the axon or dendrite has been formed their orientation changes based in extrinsic cues aka axons happen in one direction and dendrites in other way so these are cortical pyramidal neurons in vivo
In vitro what determines whether a process becomes an axon or dendrite?
neurons grown on laminin acquire polarity since the axon grows on it but the dendrites and cell body is averse to it
What attracts growing dendrites?
semaphorins - they are a class of secreted molecules and are proteins that work in gradient but they work much later in development and operate for axon guidance - high semaphorins attracts growing dendrites so a mutant of sem3a the cell bodies and axons are in the right place but the dendrites are not
How is dendritic branching developed?
the morphology is preserved meaning their is intrinsic information about their shape because their patterns in culture are strikingly similar to those in vivo
-INTRINSIC TRANSCRIPTION FACTORS PLAY A KEY IN DETERMINING DENDRITIC ARBORIZATION AND COMPLEXITY
How does dendritic tiling happen?
Dscam or down syndrome cell adhesion molecule can be alternatively spliced to generate over 36,000 isoforms which mediate self recognition and avoidance of dendrites
What are the three main domains of the growth cone?
- filopodia sense chemical signals like finger and nose
- lamellipodia membrane movement
- central core rich in organelles and mitochondria
Where are actin and tubulin concentrated in the growth cone?
actin - lamellipodia and filopodia
tubulin - central core
What two things does the growth cone do?
-receives directional cues from the environment
-is also a motor structure whose activity drives elongation
What does the growth cone integrate to regulate the cytoskeleton to guide pathfinding?
positive and negative signals
how are growth cones extended?
adhesion drives actin filament nucleation providing a substrate for additional factors and membrane exocytosis to drive forward movement
- a filopodium contacts an adhesive cue and contracts which pulls the growth cone forward
- actin filaments assemble at the leading edge of a filopodium disassemble at the trailing edge and interact with myosin along the way
- actin polymerization pushes the filopodium forward
- force generated by the retrograde flow of actin pushes the filopodium forward
Summary
