Paxillin is required for proper spinal motor axon growth into the limb

Wan-Ling Tsai, Chih-Ju Chang, Chih-Yang Wang, Tsung-I Hsu, Ming-Yuan Chang, Yi-Hsin Wu, Pei-Shan Chang, Kai-Lun Lin, Jian-Ying Chuang, Artur Kania, Tzu-Jen Kao

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

To assemble the functional circuits of the nervous system, the neuronal axonal growth cones must be precisely guided to their proper targets, which can be achieved through cell-surface guidance receptor activation by ligand binding in the periphery. We investigated the function of paxillin, a focal adhesion protein, as an essential growth cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show paxillin expression in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Paxillin loss-offunction and gain-of-function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axon trajectory selection, demonstrating an essential role of paxillin in motor axon guidance. In addition, a neuron-specific paxillin deletion in mice led to LMC axon trajectory selection errors. We also show that knocking down paxillin attenuates the growth preference of LMC neurites against ephrins in vitro, and erythropoietin-producing human hepatocellular (Eph)-mediated retargeting of LMC axons in vivo, suggesting paxillin involvement in Eph-mediated LMC motor axon guidance. Finally, both paxillin knockdown and ectopic expression of a nonphosphorylable paxillin mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating paxillin as a Src target in Eph signal relay in this context. In summary, our findings demonstrate that paxillin is required for motor axon guidance and suggest its essential role in the ephrin-Eph signaling pathway resulting in motor axon trajectory selection.

Original languageEnglish
Pages (from-to)3808-3821
Number of pages14
JournalJournal of Neuroscience
Volume41
Issue number17
Early online dateMar 16 2021
DOIs
Publication statusPublished - Apr 28 2021

Keywords

  • Axon guidance
  • Motor neuron
  • Paxillin
  • Spinal cord
  • MicroRNAs/genetics
  • Neurites/physiology
  • Mutation/genetics
  • Humans
  • Axon Guidance/physiology
  • Electroporation
  • Male
  • Chick Embryo
  • Ephrins/physiology
  • Gene Knockdown Techniques
  • Spinal Cord/cytology
  • Animals
  • Axons/physiology
  • Motor Neurons/physiology
  • Female
  • Genes, src/genetics
  • Mice
  • Paxillin/physiology

ASJC Scopus subject areas

  • Neuroscience(all)

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