Dopamine from the Brain Promotes Spinal Motor Neuron Generation during Development and Adult Regeneration

Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal. [Display omitted] •Descending dopaminergic axons control neurogenesis in the ventral spinal cord•Dopamine promotes motor neuron generation at the expense of V2 neurons•Dopamine acts through the D4a receptor and hedgehog pathway•Dopamine promotes adult motor neuron regeneration Dopaminergic axons descend from the brain and terminate in the spinal cord. Here, Reimer et al. show that dopamine release in the spinal cord promotes the production of motor neurons at the expense of V2 interneurons. This action is mediated by the hedgehog pathway via the D4a receptor.