Fig. 6.

Loss of P-cadherin causes precocious branching morphogenesis in Matrigel and enhanced, sustained dissemination into collagen I. (A and B) Representative frames from DIC time-lapse movies of (A) control [P-cadherin^+/+ (P-cad^+/+)] and (B) P-cadherin^−/− (P-cad^−/−) epithelium grown in parallel in Matrigel. (C) Percent of P-cad^+/− and P-cad^−/− organoids branching in Matrigel on day 7. n, total number of organoids counted (three biological replicates; *P = 0.04; Student’s t test, two-tailed, unequal variance). (D and E) Representative frames from DIC time-lapse movies of P-cad^+/− (D) and P-cad^−/− (E) epithelium grown in parallel in collagen I. Arrowheads indicate persistent cell dissemination. (F) Distribution of number of disseminated cells per organoid in P-cad^+/− and P-cad^−/− epithelia. n, total number of movies (three biological replicates; *P < 0.0001; upper one-sided χ² test). (G) Representative frames from a confocal time-lapse movie of P-cad^+/−, mT/mG, K14::Actin-GFP epithelium in collagen I. Arrows indicate transient, myoepithelial-led protrusions. Arrowhead indicates a single disseminated myoepithelial cell. (H) Representative frames from a confocal time-lapse movie of enhanced myoepithelial dissemination into collagen I by P-cad^−/−, mT/mG, K14::Actin-GFP epithelium. (I) Proliferation of a disseminated P-cad^−/− myoepithelial cell.