RRC ID 64769
著者 Mizoguchi T, Fukada M, Iihama M, Song X, Fukagawa S, Kuwabara S, Omaru S, Higashijima SI, Itoh M.
タイトル Transient activation of the Notch-her15.1 axis plays an important role in the maturation of V2b interneurons.
ジャーナル 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.
巻・号 147(16)
公開日 2020-8-27
DOI 10.1242/dev.191312
PII 147/16/dev191312
PMID 32855202
MeSH Animals Axons / metabolism* GABAergic Neurons / metabolism* Interneurons / metabolism* Receptors, Notch / genetics Receptors, Notch / metabolism* Signal Transduction* Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 5.611
リソース情報
ゼブラフィッシュ Tg(vsx1:GFP), T(scl:GFP), RIKEN WT, hspGFFDMC72A