However, our studies argue that the highest Rspo levels induce the development of undifferentiated and basal-only structures, together with squamous metaplasia, as characteristic of MMTV-Wnt1-driven mammary tumours in vivo. This interesting observation suggests that a ‘just right' level of Wnt signalling may be necessary for normal mammary development in which differentiated luminal and basal cells are present within the same structures48, in contrast to other tissues (for example, the intestine), which require high levels of R-spondin 1 for long-term 3D in vitro culture. Here, RSPO1 is linked to breast cancer.