Wnt-Notch signalling crosstalk in development and disease

The Notch and Wnt pathways are two of only a handful of highly conserved signalling pathways that control cell-fate decisions during animal development (Pires-daSilva and Sommer in Nat Rev Genet 4: 39-49, 2003). These two pathways are required together to regulate many aspects of metazoan development, ranging from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635-639, 2011) to the formation and patterning of the fly wing (Axelrod et al in Science 271:1826-1832, 1996; Micchelli et al in Development 124:1485-1495, 1997; Rulifson et al in Nature 384:72-74, 1996), the spacing of the ciliated cells in the epidermis of frog embryos (Collu et al in Development 139:4405-4415, 2012) and the maintenance and turnover of the skin, gut lining and mammary gland in mammals (Clayton et al in Nature 446:185-189, 2007; Clevers in Cell 154:274-284, 2013; Doupe et al in Dev Cell 18:317-323, 2010; Lim et al in Science 342:1226-1230, 2013; Lowell et al in Curr Biol 10:491-500, 2000; van et al in Nature 435:959-963, 2005; Yin et al in Nat Methods 11:106-112, 2013). In addition, many diseases, including several cancers, are caused by aberrant signalling through the two pathways (Bols et al in Endocr Rev 28: 339-363, 2007; Clevers in Cell 127: 469-480, 2006). In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease.