Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jochen Ohnmacht - , University of Edinburgh, University of Lübeck (Author)
  • Yujie Yang - , University of Edinburgh (Author)
  • Gianna W. Maurer - , University of Edinburgh (Author)
  • Antón Barreiro-Iglesias - , University of Edinburgh (Author)
  • Themistoklis M. Tsarouchas - , University of Edinburgh (Author)
  • Daniel Wehner - , University of Edinburgh (Author)
  • Dirk Sieger - , University of Edinburgh (Author)
  • Catherina G. Becker - , University of Edinburgh (Author)
  • Thomas Becker - , University of Edinburgh (Author)

Abstract

In adult zebrafish, relatively quiescent progenitor cells show lesioninduced generation of motor neurons. Developmental motor neuron generation from the spinal motor neuron progenitor domain (pMN) sharply declines at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated from the same domain. We demonstrate here that within 48 h of a spinal lesion or specific genetic ablation of motor neurons at 72 hpf, the pMN domain reverts to motor neuron generation at the expense of oligodendrogenesis. By contrast, generation of dorsal Pax2-positive interneurons was not altered. Larval motor neuron regeneration can be boosted by dopaminergic drugs, similar to adult regeneration. We use larval lesions to show that pharmacological suppression of the cellular response of the innate immune system inhibits motor neuron regeneration. Hence, we have established a rapid larval regeneration paradigm. Either mechanical lesions or motor neuron ablation is sufficient to reveal a high degree of developmental flexibility of pMN progenitor cells. In addition, we show an important influence of the immune system on motor neuron regeneration from these progenitor cells.

Details

Original languageEnglish
Pages (from-to)1464-1474
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number9
Publication statusPublished - May 2016
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 26965370

Keywords

Keywords

  • Dopamine, Hb9, Macrophage, Microglia, Nitroreductase, Olig2, Sox10