The role of serotonin in motor neuron development and regeneration

运动神经元是调节从大脑到肌肉的所有运动信号的细胞类型。在神经退行性疾病中，如ALS，这些细胞丢失，导致患者瘫痪和死亡。我们之前已经证明，与人类不同，成年斑马鱼可以替换脊髓中存在的干细胞中丢失的神经元。尽管成年哺乳动物拥有这些细胞，在发育过程中产生运动神经元，但在成年阶段，它们显然没有接收到运动神经元分化的正确信号。我们研究了神经递质5 -羟色胺在斑马鱼运动神经元发育和再生中的作用。我们发现5 -羟色胺刺激胚胎中的运动神经元发育，现在我们想测试在成人再生过程中是否也是如此。我们还将确定血清素作用所必需的受体分子。我们之前已经证明，斑马鱼胚胎中参与运动神经元发育的信号对人类干细胞产生的运动神经元具有类似的作用。这表明斑马鱼的结果与人类的情况有关。因此，我们的目标是通过将可移植或内源性干细胞分化为运动神经元来阐明一种新的信号，这种信号最终可能被利用来取代ALS中的运动神经元。

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.