The role of serotonin in motor neuron development and regeneration

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Motor neurons are the cell type that mediates all movement signals from the brain to the muscles. In neurodegenerative diseases, such as ALS, these cells are lost, leading to paralysis and death of patients. We have previously shown that, in contrast to humans, adult zebrafish can replace lost neurons from stem cells that are present in the spinal cord. Although adult mammals possess these cells, which give rise to motor neurons during development, they apparently to not receive the right signals for motor neuron differentiation at the adult stage. We study the role of the neurotransmitter serotonin in development and regeneration of motor neurons in zebrafish. We found that serotonin stimulates motor neuron development in embryos and we now want to test whether this is also the case during adult regeneration. We will also identify the receptor molecules necessary for the action of serotonin. We have previously shown that signals involved in motor neuron development in zebrafish embryos have similar actions on motor neuron generation from human stem cells. This indicates that results from zebrafish are relevant to the human situation. Thus we aim to elucidate a new signal that could ultimately be harnessed to replace motor neurons in ALS, by differentiating transplantable or endogenous stem cells into motor neurons.