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

Development. 2015 Jul 1;142(13):2291-303. doi: 10.1242/dev.125237. Epub 2015 May 20.


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.

Keywords: Chick; Cilia; Embryo; Floor plate; Mouse; Notch; Notochord; P3 progenitors; Shh.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / metabolism*
  • Biomarkers / metabolism
  • Cell Lineage
  • Chick Embryo
  • Cilia / metabolism*
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / metabolism*
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Motor Neurons / metabolism
  • NIH 3T3 Cells
  • Nerve Tissue Proteins / metabolism
  • Neural Plate / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neural Tube / metabolism
  • Notochord / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Smoothened Receptor
  • Zinc Finger Protein Gli3


  • Avian Proteins
  • Biomarkers
  • Gli3 protein, mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Notch
  • Shh protein, mouse
  • Smo protein, mouse
  • Smoothened Receptor
  • Zinc Finger Protein Gli3