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Updated: Jul 15, 2025
Assaying the Ability of Diffusible Signaling Molecules to Reorient Embryonic Spinal Commissural Axons
Published on: March 8, 2010
Cables1 links Slit/Robo and Wnt/Frizzled signaling in commissural axon guidance
Nikole R Zuñiga1,2, Alexandre Dumoulin1,2,3, Giuseppe Vaccaro1,2
1Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Abstract:
During neural circuit formation, axons navigate from one intermediate target to the next, until they reach their final target. At intermediate targets, axons switch from being attracted to being repelled by changing the guidance receptors on the growth cone surface. For smooth navigation of the intermediate target and the continuation of their journey, the switch in receptor expression has to be orchestrated in a precisely timed manner. As an alternative to changes in expression, receptor function could be regulated by phosphorylation of receptors or components of signaling pathways. We identified Cables1 as a linker between floor-plate exit of commissural axons, regulated by Slit/Robo signaling, and the rostral turn of post-crossing axons, regulated by Wnt/Frizzled signaling. Cables1 localizes β-catenin, phosphorylated at tyrosine 489 by Abelson kinase, to the distal axon, which in turn is necessary for the correct navigation of post-crossing commissural axons in the developing chicken spinal cord.
Insights
Cables1 links Slit/Robo and Wnt/Frizzled signaling pathways to guide developing axons. It ensures proper navigation of post-crossing axons by localizing phosphorylated beta-catenin to the distal axon.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Axon guidance is crucial for neural circuit formation.
- Axons navigate by switching between attraction and repulsion at intermediate targets.
- This switch requires precise temporal regulation of guidance receptor expression or function.
Purpose of the Study:
- To identify molecular mechanisms linking distinct axon guidance signaling pathways.
- To elucidate the role of Cables1 in commissural axon navigation.
- To understand how receptor function is regulated during axon pathfinding.
Main Methods:
- Immunohistochemistry in chicken spinal cord.
- Axon tracing techniques.
- Analysis of gene and protein localization.
- Phosphorylation site analysis of beta-catenin.
Main Results:
- Cables1 acts as a molecular linker between Slit/Robo and Wnt/Frizzled signaling.
- Cables1 facilitates the rostral turn of post-crossing commissural axons.
- Cables1 localizes tyrosine 489 phosphorylated beta-catenin to the distal axon.
- This localization is essential for correct axon navigation.
Conclusions:
- Cables1 plays a critical role in coordinating axon guidance.
- Regulation of receptor function via phosphorylation is a key mechanism in axon pathfinding.
- Cables1 integrates signals from different guidance cues for precise axon navigation.
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