title: Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration.
abstract: 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.
authors.affiliation: Centre for Neuroregeneration, School of Biomedical Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Michell M
authors.initials: MM
authors.lastname: Reimer
authors.forename: Anneliese
authors.initials: A
authors.lastname: Norris
authors.forename: Jochen
authors.initials: J
authors.lastname: Ohnmacht
authors.forename: Rickie
authors.initials: R
authors.lastname: Patani
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhong
authors.forename: Tatyana B
authors.initials: TB
authors.lastname: Dias
authors.forename: Veronika
authors.initials: V
authors.lastname: Kuscha
authors.forename: Angela L
authors.initials: AL
authors.lastname: Scott
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Chen
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rozov
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Frazer
authors.forename: Cameron
authors.initials: C
authors.lastname: Wyatt
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Higashijima
authors.forename: E Elizabeth
authors.initials: EE
authors.lastname: Patton
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Catherina G
authors.initials: CG
authors.lastname: Becker
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000166:cytology*; D009154:Mutation; D012038:Regeneration; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development
chemical_list: D053823:Hedgehog Proteins; D004298:Dopamine