Symmetry-breaking in branching epithelia: cells on micro-patterns under flow challenge the hypothesis of positive feedback by a secreted autocrine inhibitor of motility

Abstract

Branching morphogenesis of epithelia involves division of cells into leader (tip) and follower (stalk) cells. Published work on cell lines in culture has suggested that symmetry-breaking takes place via a secreted autocrine inhibitor of motility, the inhibitor accumulating more in concave regions of the culture boundary, slowing advance of cells there, and less in convex areas, allowing advance and a further exaggeration of the concave/convex difference. Here we test this hypothesis using a two-dimensional culture system that includes strong flow conditions to remove accumulating diffusible secretions. We find that, while motility does indeed follow boundary curvature in this system, flow makes no difference: this challenges the hypothesis of control by a diffusible secreted autocrine inhibitor.