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

Michell M Reimer, Anneliese Norris, Jochen Ohnmacht, Rickie Patani, Zhen Zhong, Tatyana B Dias, Veronika Kuscha, Angela L Scott, Yu-Chia Chen, Stanislav Rozov, Sarah L Frazer, Cameron Wyatt, Shin-Ichi Higashijima, E Elizabeth Patton, Pertti Panula, Siddharthan Chandran, Thomas Becker, Catherina G Becker

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)478–491
JournalDevelopmental Cell
Issue number5
Early online date22 May 2013
Publication statusPublished - 10 Jun 2013


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