An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation

Yun Kyoung Ryu, Sarah Ellen Collins, Hsin-Yi Henry Ho, Haiqing Zhao, Rejji Kuruvilla

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


During nervous system development, axon branching at nerve terminals is an essential step in the formation of functional connections between neurons and target cells. It is known that target tissues exert control of terminal arborization through secretion of trophic factors. However, whether the in-growing axons themselves produce diffusible cues to instruct target innervation remains unclear. Here, we use conditional mutant mice to show that Wnt5a derived from sympathetic neurons is required for their target innervation in vivo. Conditional deletion of Wnt5a resulted in specific deficits in the extension and arborization of sympathetic fibers in their final target fields, while no defects were observed in the overall tissue patterning, proliferation, migration or differentiation of neuronal progenitors. Using compartmentalized neuronal cultures, we further demonstrate that the Ror receptor tyrosine kinases are required locally in sympathetic axons to mediate Wnt5a-dependent branching. Thus, our study suggests an autocrine Wnt5a-Ror signaling pathway that directs sympathetic axon branching during target innervation.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalDevelopmental Biology
Issue number1
StatePublished - May 1 2013
Externally publishedYes


  • Autocrine Wnt signaling
  • Axon branching
  • Conditional mouse mutants
  • Sympathetic neural development

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology


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