Dissecting successful spinal cord regeneration in adult zebrafish

成年斑马鱼有惊人的能力，恢复游泳功能后，完全脊髓损伤。在哺乳动物中，这种病变会导致完全和永久性瘫痪。斑马鱼的成功脊髓再生是一个高度复杂的过程，涉及大脑中神经元的长过程（轴突）（将运动命令从大脑传递到脊髓），脊髓中的运动神经元（使其轴突朝向肌肉目标生长并引起其收缩），以及脊髓中的中间神经元（协调来自大脑的输入）。我们之前已经证明，切断的轴突形成大脑再生，被破坏的运动神经元被新的运动神经元所取代，脊髓中间神经元可能会改变它们的连接，以适应来自大脑的改变的输入。为了确定这些不同的再生成分是如何相互联系的，我们设计了减少或增强脊髓运动神经元再生的方法。因此，我们可以问脊髓运动神经元再生的作用是什么游泳的恢复，从大脑轴突的再生和脊髓中间神经元的连接。此外，我们通过分析干细胞分化的一个重要信号通路的功能，探讨了成体脊髓干细胞再生运动神经元的分子机制。通过阐明成功的斑马鱼脊髓再生，我们的目标是确定从分子到系统水平的脊髓损伤或运动神经元疾病后的功能恢复所必需的组件。

Adult zebrafish have the amazing capacity to regain swimming function after a complete spinal lesion. In mammals, such lesions lead to complete and permanent paralysis. Successful spinal cord regeneration in zebrafish is a highly complex process involving long processes (axons) of neurons in the brain (which convey movement commands from the brain to the spinal cord), motor neurons in the spinal cord (which grow their axons towards muscle targets and cause their contraction), as well as interneurons in the spinal cord (which coordinate the input from the brain). We have previously shown that severed axons form the brain regrow, that destroyed motor neurons are replaced by new motor neurons and that spinal interneurons may change their connections in order to adapt to altered input from the brain. In order to determine how these different components of regeneration are interconnected, we devised ways to reduce or enhance regeneration of spinal motor neurons. Thus we can ask what the role of spinal motor neuron regeneration is for recovery of swimming, for regrowth of axons from the brain and for connections of spinal interneurons. Moreover, we address the molecular mechanism of motor neuron regeneration from adult spinal stem cells by analysing the function of an important signalling pathway for stem cell differentiation. By elucidating successful spinal cord regeneration in zebrafish, we aim to identify the components necessary for a return of function after a spinal lesion or motor neuron disease from the molecular to the systems level.