期刊
DEVELOPMENTAL CELL
卷 25, 期 5, 页码 478-491出版社
CELL PRESS
DOI: 10.1016/j.devcel.2013.04.012
关键词
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资金
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Robert Packard Center for ALS research at Johns Hopkins
- Euan MacDonald Centre for Motor Neurone Disease (MND) Research
- College of Medicine and Veterinary Medicine BioQuarter IP Development grant
- Medical Research Council
- Overseas Research Studentship awards
- BBSRC PhD studentship
- MND Scotland PhD studentship
- EMBO long-term fellowship
- Sir David Walker Fellowship
- Beverley and Raymond Sackler Scholarship
- Wellcome Trust Clinical Research Training Fellowship
- Academy of Finland
- Sigrid Juselius Foundation
- Biotechnology and Biological Sciences Research Council [BB/H003304/1] Funding Source: researchfish
- Medical Research Council [G120/875, MC_U127585840, MC_PC_U127585840] Funding Source: researchfish
- BBSRC [BB/H003304/1] Funding Source: UKRI
- MRC [MC_PC_U127585840, MC_U127585840, G120/875] Funding Source: UKRI
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.
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