1. A conserved role for Notch signaling in priming the cellular response to Shh through ciliary localisation of the key Shh transducer Smo
- Author
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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, and J Kim, Dale
- Subjects
Neural Tube ,animal structures ,Notch ,Mouse ,Kruppel-Like Transcription Factors ,Notochord ,Nerve Tissue Proteins ,Chick Embryo ,Chick ,Shh ,P3 progenitors ,Receptors, G-Protein-Coupled ,Avian Proteins ,Mice ,Neural Stem Cells ,Zinc Finger Protein Gli3 ,Animals ,Cell Lineage ,Hedgehog Proteins ,Cilia ,Motor Neurons ,Neural Plate ,Receptors, Notch ,Gene Expression Regulation, Developmental ,Fibroblasts ,Smoothened Receptor ,Embryo ,embryonic structures ,NIH 3T3 Cells ,Biomarkers ,Floor plate ,Signal Transduction ,Research Article - 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., Highlighted article: Shh signalling controls dorso-ventral cell fate in the neural tube. Notch regulates ciliary architecture and localisation of key Shh pathway components, thus sensitising cells to Shh.
- Published
- 2015