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Focus on the process of axon guidance
Learning objectives:
  - Describe how axons are guided to their targets
  - Types of cues that guide axons
  - How growth cones respond to environmental cues
  - Example of dynamic changes in a neuron facilitating axonal pathfinding
Example to be discussed: axon crossing the midline

Neurons must extend processes from their cell bodies to connect with other neurons or muscle cells.
Initial step: neurons polarize and send out one protrusion which develops into a growth cone.
Definition of growth cone:
- Located at the end of the developing axon.
- Functions similarly to fingers at the end of a hand, guiding the developing axon to its target site.
Formation of synapses occurs once axons reach their targets.
Formation of dendrites occurs at the opposite side of the neuron for receiving input from other neurons.

Neurons utilize growth cones to locate their target sites without visual cues.
Growth cone receptors detect signals in the environment, both:
  - Diffusive signals:
    - Secreted molecules diffusing around the area.
  - Contact signals:
    - Mediated by other cells or extracellular matrix molecules.
The structure of a growth cone includes:
  - Actin-rich protrusions (lamellipodia and filopodia) which aid in movement.
  - Microtubules present inside the growth cone that provide structure and support.

Axon guidance cues can be categorized into:
- Attractive cues: Promote growth towards a target.
- Repulsive cues: Induce movement away from a source.
Cues can act over two ranges:
  - Long-range cues:
    - Soluble and diffusing through embryonic tissues (example: pleasant smells attracting axons).
  - Short-range cues:
    - Contact-based signals (example: axons repelled or attracted when in direct contact).
Mechanisms:
- Growth cones are equipped with numerous receptors to respond to environmental signals.
- Different axons express varying receptors responding to specific cues.

Intracellular changes in response to cues affect growth cone behavior.
Cues can lead to:
- Polymerization: Growth towards a signal (microtubules lengthened).
- Depolymerization: Movement away from a signal (microtubules shortened).
Microfilaments also go through similar processes:
- Can be polymerized or depolymerized, influencing growth cone movement.
Pioneer axons:
- First axons to grow out, providing a path for subsequent axons.
- Utilize cell adhesion to guide newer axons by expressing appropriate molecules to adhere to previously grown axons.

Mapping with Repulsive Cues:
- Some axonal connections help to create maps in the brain (corresponding to sensory inputs).
- Maps organize neuron functions (e.g., motor control regions).
Gradient Expression Example:
- Involves a repulsive cue, the F receptor, with varied expression levels across eye regions.
- High F receptor expression results in repulsion from certain regions—visual patterns and connections are subsequently organized based on receptor levels.

Define decussation:
- The concept that the left side of the brain controls the right side of the body.
Importance of precise axon crossing at the midline (once crossing over, they should not recross).
Key proteins involved:
- Slit: Expressed along the midline to prevent recrossing.
- Robo: The receptor for slit, expressed on either side of the midline.
Effects of knocking out slit:
- Axons approach the midline but fail to leave it, indicating the significance of repulsion in guidance.
Drosophila Example of Midline Crossing:
- Growth cones attracted to the midline initially via netrin binding.
- Increased interaction with netrin leads to downregulation of COM, allowing robo receptor expression to occur at the cell surface, causing repulsion to prevent recrossing the midline.
Mechanism highlights the timing of receptor expression as crucial in mediating axon guidance.