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

TY - JOUR

T1 - A conserved role for Notch in priming the cellular response to Shh through ciliary localisation of the key Shh transducer, Smoothened

AU - Stasiulewicz, Magdalena

AU - Gray, Shona

AU - Mastromina, Ioanna

AU - Silva, Joana Clara

AU - Bjorklund, Mia

AU - Seymour, Philip A

AU - Booth, David

AU - Thompson, Calum

AU - Green, Rich

AU - Hall, Emma A

AU - Serup, Palle

AU - Dale, J Kim

N1 - © 2015. Published by The Company of Biologists Ltd.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

U2 - 10.1242/dev.125237

DO - 10.1242/dev.125237

M3 - Journal article

C2 - 25995356

SN - 0950-1991

VL - 142

SP - 2291

EP - 2303

JO - Development

JF - Development

ER -