Dissecting successful spinal cord regeneration in adult zebrafish

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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.