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Abstract
SummaryIn 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.
Highlights
In contrast to mammals (Ohori et al, 2006; Su et al, 2014), the CNS of fishes and salamanders regenerates neurons after injury
Regeneration of spinalintrinsic serotonergic interneurons was unaltered by these manipulations
Motor neurons are regenerated from a ventro-lateral motor neuron progenitor-like domain of Ependymo-radial glial cells (ERGs), identified by olig2 expression, after spinal cord transection, whereas serotonergic neurons are regenerated from a more-ventral ERG domain (Kuscha et al, 2012a)
Summary
In contrast to mammals (Ohori et al, 2006; Su et al, 2014), the CNS of fishes and salamanders regenerates neurons after injury. In the spinal cord of adult zebrafish, ERGs are arranged in dorso-ventral domains, similar to progenitors in development (Dessaud et al, 2008), and give rise to distinct cell types after lesion (Kuscha et al, 2012a, 2012b; Reimer et al, 2008). Similar ventricular progenitors with the potential to generate neurons exist in the mammalian spinal cord, but in vivo, these cells only give rise to glia (Meletis et al, 2008). Because of the amazing regenerative capacity of ERGs in zebrafish, it is important to identify the signals that orchestrate neuronal regeneration from these cells. Dopamine, derived exclusively from descending axons from the diencephalon, is a remote signal promoting motor neuron development and regeneration (Reimer et al, 2013)
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