PUBLICATION

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

Authors
Reimer, M.M., Norris, A., Ohnmacht, J., Patani, R., Zhong, Z., Dias, T.B., Kuscha, V., Scott, A.L., Chen, Y.C., Rozov, S., Frazer, S.L., Wyatt, C., Higashijima, S., Patton, E.E., Panula, P., Chandran, S., Becker, T., and Becker, C.G.
ID
ZDB-PUB-130703-35
Date
2013
Source
Developmental Cell   25(5): 478-491 (Journal)
Registered Authors
Becker, Catherina G., Becker, Thomas, Chen, Yu-Chia, Dias, Tatyana, Kuscha, Veronika, Norris, Anneliese, Ohnmacht, Jochen, Panula, Pertti, Patton, E. Elizabeth, Reimer, Michell M., Scott, Angela
Keywords
none
MeSH Terms
  • Brain/embryology*
  • Brain/metabolism*
  • Interneurons/metabolism
  • Time Factors
  • Signal Transduction
  • Motor Neurons/cytology*
  • Spinal Cord/cytology
  • Animals
  • Stem Cells/cytology
  • Dopamine/metabolism*
  • Regeneration*
  • Microscopy, Fluorescence
  • Hedgehog Proteins/metabolism
  • Gene Expression Regulation, Developmental*
  • Mutation
  • Zebrafish/embryology
  • Zebrafish/growth & development
  • Immunohistochemistry
(all 18)
PubMed
23707737 Full text @ Dev. Cell
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.

Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b577
    Point Mutation
    c264TgTransgenic Insertion
      cf3TgTransgenic Insertion
        e1TgTransgenic Insertion
          m866
            Small Deletion
            ml2TgTransgenic Insertion
              nns5TgTransgenic Insertion
                rw0TgTransgenic Insertion
                  s300tTgTransgenic Insertion
                    vu12TgTransgenic Insertion
                      1 - 10 of 12
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      drd4aMO1-drd4aMRPHLNO
                      drd4aMO2-drd4aMRPHLNO
                      gli2bMO1-gli2bMRPHLNO
                      thMO3-thMRPHLNO
                      1 - 4 of 4
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                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-foxn4polyclonal
                        Rabbit
                        Ab1-mnx1monoclonal
                          IgG1Mouse
                          Ab1-olig2polyclonal
                            Rabbit
                            Ab2-nkx6monoclonalIgG1Mouse
                            Ab3-thmonoclonalIgG1Mouse
                            1 - 5 of 5
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                            Orthology
                            No data available
                            Engineered Foreign Genes
                            Marker Marker Type Name
                            DsRed2EFGDsRed2
                            EGFPEFGEGFP
                            GAL4EFGGAL4
                            GFPEFGGFP
                            mCherryEFGmCherry
                            NTREFGNTR
                            1 - 6 of 6
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                            Mapping
                            No data available