title: Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish.
abstract: In adult zebrafish, relatively quiescent progenitor cells show lesion-induced 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.
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Jochen
authors.initials: J
authors.lastname: Ohnmacht
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Gianna W
authors.initials: GW
authors.lastname: Maurer
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Antón
authors.initials: A
authors.lastname: Barreiro-Iglesias
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Themistoklis M
authors.initials: TM
authors.lastname: Tsarouchas
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehner
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sieger
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK catherina.becker@ed.ac.uk thomas.becker@ed.ac.uk.
authors.forename: Catherina G
authors.initials: CG
authors.lastname: Becker
authors.affiliation: Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK catherina.becker@ed.ac.uk thomas.becker@ed.ac.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007814:Larva / Q000166:cytology* / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D008795:Metronidazole / Q000494:pharmacology; D017628:Microglia / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology; D051762:PAX2 Transcription Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D051762:PAX2 Transcription Factor; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish; D008795:Metronidazole; D003907:Dexamethasone
keywords: Dopamine; Hb9; Macrophage; Microglia; Nitroreductase; Olig2; Sox10