02 June 2015
A conserved role for Notch in priming the cellular response to Shh through ciliary localisation of the key Shh transducer, Smoothened
Stasiulewicz, Magdalena, Shona Gray, Ioanna Mastromina, Joana Clara Silva, Mia Bjorklund, Philip A. Seymour, David Booth, Calum Thompson, Rich Green, Emma A. Hall, Palle Serup & J. Kim Dale (2015). A conserved role for Notch in priming the cellular response to Shh through ciliary localisation of the key Shh transducer, Smoothened. Development, doi:10.1242/dev.125237 (epub ahead of print on May 20, 2015).
Notochord-derived Sonic Hedgehog (SHH) is essential for dorso-ventral 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 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.