Serotonin Promotes Development and Regeneration of Spinal Motor Neurons in Zebrafish
Antón Barreiro-Iglesias,
Karolina S. Mysiak,
Angela L. Scott,
Michell M. Reimer,
Yujie Yang (杨宇婕),
Catherina G. Becker,
Thomas Becker
Affiliations
Antón Barreiro-Iglesias
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Karolina S. Mysiak
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Angela L. Scott
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Michell M. Reimer
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Yujie Yang (杨宇婕)
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Catherina G. Becker
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
Thomas Becker
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor’s Building, University of Edinburgh, Edinburgh EH16 4SB, UK
In contrast to mammals, zebrafish regenerate spinal motor neurons. During regeneration, developmental signals are re-deployed. Here, we show that, during development, diffuse serotonin promotes spinal motor neuron generation from pMN progenitor cells, leaving interneuron numbers unchanged. Pharmacological manipulations and receptor knockdown indicate that serotonin acts at least in part via 5-HT1A receptors. In adults, serotonin is supplied to the spinal cord mainly (90%) by descending axons from the brain. After a spinal lesion, serotonergic axons degenerate caudal to the lesion but sprout rostral to it. Toxin-mediated ablation of serotonergic axons also rostral to the lesion impaired regeneration of motor neurons only there. Conversely, intraperitoneal serotonin injections doubled numbers of new motor neurons and proliferating pMN-like progenitors caudal to the lesion. Regeneration of spinal-intrinsic serotonergic interneurons was unaltered by these manipulations. Hence, serotonin selectively promotes the development and adult regeneration of motor neurons in zebrafish.
