sensory neuron axon guidance

Definition

Target type: biologicalprocess

The process in which the migration of an axon growth cone of a sensory neuron is directed to a specific target site in response to a combination of attractive and repulsive cues. A sensory neuron is an afferent neuron conveying sensory impulses. [CL:0000101, GOC:pr]

Sensory neuron axon guidance is a complex and tightly regulated process that ensures the precise wiring of the nervous system. It involves a series of intricate molecular interactions and cellular signaling events, leading to the directed growth of sensory neuron axons to their appropriate target cells. The process can be divided into several stages:

1. **Axon initiation and polarization:** Sensory neuron axons emerge from the cell body as a specialized growth cone, a dynamic structure that acts as the sensing and navigating unit of the axon. This growth cone is characterized by its highly motile, finger-like extensions called filopodia and lamellipodia.

2. **Long-range guidance:** Axons navigate through the developing nervous system using a combination of attractive and repulsive cues. These cues can be either secreted molecules, such as netrins and semaphorins, or cell surface molecules, such as ephrins and their receptors.

- **Attractive cues:** Netrins, for example, promote axon growth towards the target area by activating specific receptors on the growth cone.

- **Repulsive cues:** Semaphorins, on the other hand, repel axons from inappropriate areas by triggering intracellular signaling pathways that lead to cytoskeletal rearrangements and growth cone collapse.

3. **Target recognition and synapse formation:** Once the axon reaches its target area, it interacts with specific target cells, leading to synapse formation. This interaction is mediated by a variety of cell adhesion molecules and signaling pathways.

4. **Axon refinement and pruning:** During development, a significant amount of axonal pruning occurs. This process is necessary to remove unnecessary connections and refine the neural circuitry. Axonal pruning is regulated by a combination of factors, including competition for target cells, neurotrophic factors, and activity-dependent mechanisms.

**Molecular mechanisms:**
Sensory neuron axon guidance involves a wide range of molecular signaling pathways. These pathways include:

- **Receptor tyrosine kinases (RTKs):** RTKs, such as Eph receptors and Trk receptors, are activated by specific ligands, such as ephrins and neurotrophins, respectively. This activation triggers intracellular signaling cascades that regulate growth cone motility and guidance.

- **G protein-coupled receptors (GPCRs):** GPCRs, such as netrin receptors (DCC and UNC5) and semaphorin receptors (Plexins), are activated by secreted guidance cues. This activation leads to intracellular signaling pathways that modulate cytoskeletal dynamics and growth cone behavior.

- **Transcription factors:** Transcription factors, such as Slit2 and Robo1, play a role in regulating gene expression during axon guidance. These factors can influence the expression of guidance cues and their receptors, as well as downstream signaling molecules.

- **Cytoskeletal proteins:** Cytoskeletal proteins, such as actin and microtubules, are essential for growth cone motility and axon extension. These proteins are dynamically regulated by guidance cues, leading to changes in growth cone morphology and direction.

**Clinical relevance:**
Defects in sensory neuron axon guidance can lead to a variety of neurological disorders, including:

- **Congenital insensitivity to pain:** Mutations in genes involved in sensory neuron development can lead to a lack of pain sensation.

- **Spinal muscular atrophy:** This disorder is characterized by degeneration of motor neurons, leading to muscle weakness and atrophy.

- **Autism spectrum disorder:** Recent studies suggest that defects in axon guidance may contribute to autism spectrum disorder.

In conclusion, sensory neuron axon guidance is a complex and dynamic process that involves a wide range of molecular signaling pathways and cellular events. This process is critical for the proper development and function of the nervous system, and defects in this process can lead to a variety of neurological disorders.'"

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