An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Axon branching is vital for forming neural connections.
• Target tissues secrete factors influencing axon arborization.
• The role of axons in producing their own guidance cues is unclear.

Purpose of the Study:

• To investigate if axons produce diffusible cues for target innervation.
• To determine the role of Wnt5a in sympathetic axon branching.
• To elucidate the signaling pathway mediating Wnt5a-dependent branching.

Main Methods:

• Utilized conditional mutant mice to delete Wnt5a in sympathetic neurons.
• Employed compartmentalized neuronal cultures.
• Analyzed sympathetic fiber extension and arborization in vivo and in vitro.

Main Results:

• Conditional Wnt5a deletion caused specific deficits in sympathetic fiber extension and arborization.
• No defects were observed in neuronal progenitor patterning, proliferation, migration, or differentiation.
• Ror receptor tyrosine kinases were found to be essential locally in axons for Wnt5a-mediated branching.

Conclusions:

• Wnt5a produced by sympathetic neurons is required for their target innervation.
• An autocrine Wnt5a-Ror signaling pathway directs sympathetic axon branching.
• This pathway is crucial for establishing functional neural circuits.