Fig. 3.

Multiscale dynamics of Hippo and Wnt signalling, and Hippo-dependent contact-inhibition (CI), in wild type crypt with imposed external Wnt gradient (M_E). (a, b) Effects of Hippo-based CI on Wnt-dependent cell cycle, measuring mitotic indices (proportion of cells undergoing mitosis as a function of position in the crypt). We considered both static (M_E1, solid lines) and dynamic (M_E2, dashed lines) Wnt cell models (Wnt assigned at birth or continually updated, respectively), with Wnt signalling affecting 100% (a) or 40% (b) of the crypt. The different volumes at which cells undergo CI are indicated by blue (CI at 60% of equilibrium volume) and red (CI at 90% of equilibrium volume) lines. (c, d) Velocity whisker plots for a crypt cell population using the static (M_E1) Wnt model, and Wnt signalling affecting 100% (c) or 40% (d) of the crypt, with CI occurring at 60% volume (blue) and 90% volume (red). The box plots indicate the median velocity of the cells at increasing heights up the crypt, with the box representing the 25th and 75th percentiles respectively (Supplementary Information). The whiskers extend to the most extreme velocities recorded over the course of the 150 repeated experiments. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)