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The Slit–Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates

Summary

This review explains how growing nerve fibers find their way in the developing brain and spinal cord using special signalling molecules called Slit and Robo. These molecules work together like a navigation system, with Slit acting as a ‘stop’ signal secreted from midline structures and Robo receptors on growing axons receiving these signals. The same system is used by flies, worms, and humans, showing that this guidance mechanism is an ancient and essential part of nervous system development.

Background

The Slit-Robo signalling pathway is a fundamental mechanism in nervous system development that guides growing axons to their targets. Slit proteins are secreted guidance molecules initially identified in Drosophila melanogaster that act as chemorepellents, while Robo receptors on axonal growth cones mediate this repulsive response. This pathway is evolutionarily conserved across vertebrates and invertebrates, playing crucial roles in axonal pathfinding and neuronal migration.

Objective

This review provides a comprehensive comparative analysis of Slit-Robo signalling during nervous system development across vertebrate and invertebrate organisms. The authors examine the molecular characteristics, expression patterns, regulatory mechanisms, and signal transduction pathways of these proteins in both model systems.

Results

The review reveals that Slit and Robo proteins share conserved structural domains including leucine-rich domains and immunoglobulin domains. Expression patterns vary dynamically during development with Slit secreted from midline structures (ventral nerve cord in flies, floor plate in vertebrates) and Robo expressed on navigating axons. Multiple regulatory mechanisms including transcriptional control, post-translational modifications, and interactions with co-receptors modulate pathway activity.

Conclusion

Slit-Robo signalling represents an evolutionarily conserved axon guidance mechanism with diverse roles beyond classical repulsion, including axonal growth promotion in specific contexts. The pathway integrates with multiple regulatory proteins and signalling mechanisms to precisely control axonal pathfinding, neuronal migration, and nervous system development across vertebrate and invertebrate species.
  • Published in:Open Biology,
  • Study Type:Review,
  • Source: PMID: 40628293, DOI: 10.1098/rsob.250026
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