Axon Guidance and Growth Cones

• Axon Guidance

Introduction

• Axon guidance involves the integration of sensory and motor information in the brain.
• Nervous system connectivity is crucial for function.
• Accurate connectivity is important.
• Misconnectivity can have negative consequences.
• Mechanisms of pathfinding are becoming clearer.

Growth Cone

• Axons and dendrites have a motile sensory tip in growing neurons.
• Growth cones display dynamic behavior in vitro.
• Growth cones explore the environment for guidance cues.
• Growth cones form focal contacts for elongation.
• Knowledge about growth cones is derived from tissue culture.
• Molecular biology is uncovering the proteins involved in growth cone function.
• Live imaging techniques are used to study growth cones in vivo.
• Cytoskeleton dynamics are crucial for pathfinding.
• Microtubule and actin interaction plays a key role.
• Growth cones have three arbitrary zones.
• Actin filaments are important components.
• Microtubules are essential for growth cone function.
• Axon growth is initiated by the growth cone.
• Signal transduction is involved in growth cone guidance.

Growth Cone Guidance Mechanisms

• Chemical (chemotropism) factors guide growth cones.
• Physical cues guide growth cones.
• Electrical signals influence growth cone guidance.

Target Contact

• Excess axons retract during development.
• Target contact ensures necessary connections.
• Neurotrophins act as survival signals for neurons.
• Electrical activity promotes neuronal survival.

Key Axon Guidance Molecules

• Immunoglobulin (Ig) superfamily CAMs (cell adhesion molecules) guide axons.
• Cadherins guide axons.
• Extracellular matrix molecules guide axons.
• Netrins are axon guidance molecules.
• Slits are axon guidance molecules.
• Semaphorins are axon guidance molecules.
• Ephrins are axon guidance molecules.
• Myelin proteins guide axons.

Combinatorial Guidance Signals

• In grasshopper limbs, Semas act through physical mechanisms.
• Neural tube commissural axons are guided by:
  • BMPs
  • Semas
  • Ephrins (repulsion)
  • Netrin (attraction)
  • Slits (repulsion after crossing)

Developmental Changes and Axon Regeneration

• Immature nervous system is supportive of axon growth.
• Postnatal central nervous system is inhibitory to axon growth.
• Inhibitory molecules, like myelin, are upregulated after development.
• Slow nerve degeneration occurs in the central nervous system.
• Intrinsic neuronal changes are important for regeneration.
• cAMP activity influences axon regeneration.
• Receptor expression changes, such as semaphorin receptors in RGCs, affect axon guidance.
• Signaling molecule changes within the growth cone influence axon behavior.

Retinotectal Projection Pathway

• The retinotectal projection pathway is the best-studied pathway for axon guidance.
• It involves accurate topographical guidance from the retina to the tectum.
• Studies have been conducted in vertebrates such as frogs, chicks, and zebrafish.
• The mammalian equivalent is the projection from the superior colliculus to the LGN to the cortex.
• There are differences in the visual field overlap between mammals and other species.
• The optic chiasm involves crossing patterns of axons.
• Retinal axon growth is a key process.
• The optic nerve head (ONH) is involved in the pathway.
• The optic chiasm is a crucial structure.
• The optic tract carries visual information.
• The tectum is the target structure in the brain.