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Axon guidance at the midline choice point
Z Kaprielian1, E Runko, R Imondi
1Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, USA. kapriel@aecom.yu.edu
Summary
Specialized midline cells guide developing axons across the central nervous system (CNS) midline only once. Axon surface molecules change during crossing, altering responses to guidance cues for proper pathway formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The central nervous system (CNS) exhibits bilateral symmetry, with information transfer across the midline mediated by commissural axons.
- Axon guidance at the CNS midline is crucial for proper neural circuit formation, involving both crossing and non-crossing pathways.
- Midline cells secrete guidance cues that regulate axon navigation, ensuring axons cross the midline only once and ipsilateral axons remain on their own side.
Purpose of the Study:
- To investigate the role of specialized midline cells in guiding commissural and ipsilateral axons in the developing CNS.
- To elucidate the molecular mechanisms underlying the precise guidance of axons at the CNS midline.
- To understand how dynamic changes in axon surface molecules influence responses to guidance cues during midline crossing.
Main Methods:
- Utilized studies on developing vertebrate spinal cord and Drosophila ventral nerve cord.
- Examined interactions between guidance cues on midline cells and receptors on pathfinding axons.
- Investigated dynamic alterations in commissural axon surface molecular composition during midline traversal.
Main Results:
- Midline cells secrete attractive cues that guide commissural axons to the CNS midline.
- Short-range cell-surface interactions prevent ipsilateral axons from entering the midline and ensure commissural axons cross only once.
- Commissural axons dynamically alter surface molecules upon crossing, becoming responsive to repulsive cues and losing responsiveness to attractive cues.
Conclusions:
- Regulated guidance systems mediated by midline cells and axon surface molecule dynamics are essential for proper pathway formation.
- Conserved ligand-receptor systems control midline guidance, with modular receptors dictating ligand recognition and downstream responses.
- Significant progress has been made, but many questions remain regarding the intricate mechanisms of midline guidance.