Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

Yuto Ueda, Yuki Shimizu, Nobuyuki Shimizu, Tohru Ishitani, Toshio Ohshima

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Unlike humans and other mammals, adult zebrafish have the superior capability to recover from central nervous system (CNS) injury. We previously found that proliferation of radial glia (RG) is induced in response to stab injury in optic tectum and that new neurons are generated from RG after stab injury. However, molecular mechanisms which regulate proliferation and differentiation of RG are not well known. In the present study, we investigated Shh and Notch signaling as potential mechanisms regulating regeneration in the optic tectum of adult zebrafish. We used Shh reporter fish and confirmed that canonical Shh signaling is activated specifically in RG after stab injury. Moreover, we have shown that Shh signaling promotes RG proliferation and suppresses their differentiation into neurons after stab injury. In contrast, Notch signaling was down-regulated after stab injury, indicated by the decrease in the expression level of her4 and her6, a target gene of Notch signaling. We also found that inhibition of Notch signaling after stab injury induced more proliferative RG, but that inhibition of Notch signaling inhibited generation of newborn neurons from RG after stab injury. These results suggest that high level of Notch signaling keeps RG quiescent and that appropriate level of Notch signaling is required for generation of newborn neurons from RG. Under physiological condition, activation of Shh signaling or inhibition of Notch signaling also induced RG proliferation. In adult optic tectum of zebrafish, canonical Shh signaling and Notch signaling play important roles in proliferation and differentiation of RG in physiological and regenerative conditions.

    Original languageEnglish
    JournalJournal of Comparative Neurology
    DOIs
    Publication statusAccepted/In press - 2018 Jan 1

    Fingerprint

    Hedgehogs
    Superior Colliculi
    Neurogenesis
    Zebrafish
    Neuroglia
    Wounds and Injuries
    Neurons
    Nervous System Trauma
    Regeneration
    Mammals
    Fishes
    Central Nervous System

    Keywords

    • neurogenesis
    • notch signal
    • regeneration
    • RRID: AB_10000325
    • RRID: AB_143165
    • RRID: AB_2160651
    • RRID: AB_221448
    • RRID: AB_2534069
    • RRID: AB_2534079
    • RRID: AB_2534083
    • RRID: AB_2534091
    • RRID: AB_2536183
    • RRID: AB_302659
    • RRID: AB_591823
    • sonic hedgehog signal
    • zebrafish

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury. / Ueda, Yuto; Shimizu, Yuki; Shimizu, Nobuyuki; Ishitani, Tohru; Ohshima, Toshio.

    In: Journal of Comparative Neurology, 01.01.2018.

    Research output: Contribution to journalArticle

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    AU - Ishitani, Tohru

    AU - Ohshima, Toshio

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