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 Björklund, Philip A Seymour, David Booth, Calum Thompson, Richard J Green, Emma A Hall, Palle Serup, J Kim Dale

Research output: Contribution to journalArticlepeer-review

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 that Notch signalling augments the response of neuroepithelial cells to Shh, leading to the induction of higher expression levels of the Shh target gene Ptch1 and subsequently induction of more ventral cell fates. Furthermore, we demonstrate that activated Notch1 leads to pronounced accumulation of Smoothened (Smo) within primary cilia and elevated levels of full-length Gli3. Finally, we show that 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 that acts mechanistically via regulation of ciliary localisation of key components of its transduction machinery.

Original languageEnglish
Pages (from-to)2291-303
Number of pages13
JournalDevelopment
Volume142
Issue number13
DOIs
Publication statusPublished - 1 Jul 2015

Keywords

  • Animals
  • Avian Proteins
  • Biomarkers
  • Cell Lineage
  • Chick Embryo
  • Cilia
  • Fibroblasts
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Mice
  • Motor Neurons
  • NIH 3T3 Cells
  • Nerve Tissue Proteins
  • Neural Plate
  • Neural Stem Cells
  • Neural Tube
  • Notochord
  • Receptors, G-Protein-Coupled
  • Receptors, Notch
  • Signal Transduction

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