University of Dundee

Mechanistic investigation into the interplay between Notch and Shh signalling in cell fate choice

My lab has been working on the role of Notch signalling in diversification of neuronal identities from common progenitor pools during dorsoventral patterning of the neural tube during early stages of vertebrate embryogenesis. We showed Notch directs cell fate choice in the node. Notochord derived Sonic hedgehog signalling is essential for dorsoventral patterning of the overlying  neural tube. Increasing concentration and duration of Shh signal induces progressively more ventral cell 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 show that activated Notch1 leads to pronounced accumulation of Smoothened within primary cila and elevated levels of full length Gli3. Notch thereby augments the response of cells to Shh, by promoting Shh-independent ciliary entry of Smo and ciliary exit of Ptc. Notch dramatically increases cilia length in the neural tube and in fibroblasts and Notch mutants show a reduction in ciliary length This novel interaction of these two pathways is likely impact other developmental and disease contexts. We wish to investigate the mechanistic mechanisms underlying this crosstalk