PUBLICATION

Transient activation of the Notch-her15.1 axis plays an important role in the maturation of V2b interneurons

Authors
Mizoguchi, T., Fukada, M., Iihama, M., Song, X., Fukagawa, S., Kuwabara, S., Omaru, S., Higashijima, S.I., Itoh, M.
ID
ZDB-PUB-200829-3
Date
2020
Source
Development (Cambridge, England)   147(16): (Journal)
Registered Authors
Higashijima, Shin-ichi, Itoh, Motoyuki, Mizoguchi, Takamasa
Keywords
Axon outgrowth, GABA, Her15.1, Notch signaling, V2b interneuron, Zebrafish
MeSH Terms
  • Signal Transduction*
  • GABAergic Neurons/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Animals
  • Interneurons/metabolism*
  • Axons/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
(all 11)
PubMed
32855202 Full text @ Development
Abstract
In the vertebrate ventral spinal cord, p2 progenitors give rise to two interneuron subtypes: excitatory V2a interneurons and inhibitory V2b interneurons. In the differentiation of V2a and V2b cells, Notch signaling promotes V2b fate at the expense of V2a fate. Later, V2b cells extend axons along the ipsilateral side of the spinal cord and express the inhibitory transmitter GABA. Notch signaling has been reported to inhibit the axonal outgrowth of mature neurons of the central nervous system; however, it remains unknown how Notch signaling modulates V2b neurite outgrowth and maturation into GABAergic neurons. Here, we have investigated neuron-specific Notch functions regarding V2b axon growth and maturation into zebrafish GABAergic neurons. We found that continuous neuron-specific Notch activation enhanced V2b fate determination but inhibited V2b axonal outgrowth and maturation into GABAergic neurons. These results suggest that Notch signaling activation is required for V2b fate determination, whereas its downregulation at a later stage is essential for V2b maturation. Accordingly, we found that a Notch signaling downstream gene, her15.1, showed biased expression in V2 linage cells and downregulated expression during the maturation of V2b cells, and continuous expression of her15.1 repressed V2b axogenesis. Our data suggest that spatiotemporal control of Notch signaling activity is required for V2b fate determination, maturation and axogenesis.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
chi10TgTransgenic Insertion
    chi11TgTransgenic Insertion
      kca3TgTransgenic Insertion
        nkhspGFFDMC72AEtTransgenic Insertion
        nkuasrfp1aTgTransgenic Insertion
          nns5TgTransgenic Insertion
            nns66TgTransgenic Insertion
              1 - 7 of 7
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab1-mycmonoclonal
                		IgG1Mouse
                Ab6-gabapolyclonal
                  		Rabbit
                  1 - 2 of 2
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                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  GAL4FFEFGGAL4FF
                  GFPEFGGFP
                  RFPEFGRFP
                  1 - 3 of 3
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                  Mapping
                  No data available
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                  Citation
                  Mizoguchi, T., Fukada, M., Iihama, M., Song, X., Fukagawa, S., Kuwabara, S., Omaru, S., Higashijima, S.I., Itoh, M. (2020) Transient activation of the Notch-her15.1 axis plays an important role in the maturation of V2b interneurons. Development (Cambridge, England). 147(16):.