A conserved role for Notch signaling in priming the cellular response to Shh through ciliary localisation of the key Shh transducer, Smo

Magdalena Stasiulewicz, Shona D. Gray, Ioanna Mastromina, Joana C. Silva, Mia Bjorklund, Philip A. Seymour, David Booth, Calum Thompson, Richard J. Green, Emma A. Hall, Palle Serup, J. Kim Dale (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)

    Abstract

    Notochord-derived Sonic Hedgehog (Shh) is essential for dorsoventral patterning of the overlying neural tube. Increasing concentration and duration of Shh signal induces progenitors to acquire progressively more ventral fates. We show Notch signalling augments the response of neuroepithelial cells to Shh, leading to the induction of higher expression levels of the Shh target gene Ptc1 and subsequently induction of more ventral cell fates. Furthermore, we demonstrate activated Notch1 leads to pronounced accumulation of Smoothened (Smo) within primary cilia and elevated levels of full-length Gli3. Finally, we show Notch activity promotes longer primary cilia both in vitro and in vivo. Strikingly, these Notch-regulated effects are Shh-independent. These data identify Notch signalling as a novel modulator of Shh signalling which acts mechanistically via regulation of ciliary localisation of key components of its transduction machinery.

    Original languageEnglish
    Pages (from-to)2291-2303
    Number of pages13
    JournalDevelopment
    Volume142
    Issue number3
    Early online date20 May 2015
    DOIs
    Publication statusPublished - 1 Jul 2015

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