Transient activation of the Notch-her15.1 axis plays an important role in the maturation of V2b interneurons
- Mizoguchi, T., Fukada, M., Iihama, M., Song, X., Fukagawa, S., Kuwabara, S., Omaru, S., Higashijima, S.I., Itoh, M.
- Development (Cambridge, England) 147(16): (Journal)
- Registered Authors
- Higashijima, Shin-ichi, Itoh, Motoyuki, Mizoguchi, Takamasa
- Axon outgrowth, GABA, Her15.1, Notch signaling, V2b interneuron, Zebrafish
- MeSH Terms
- GABAergic Neurons/metabolism*
- Receptors, Notch/genetics
- Receptors, Notch/metabolism*
- Signal Transduction*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 32855202 Full text @ Development
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):.
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes