title: 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.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Martin
authors.affiliation: School of Engineering, James Watt Building, University of Glasgow, GL12 8QQ, UK.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Gregory
authors.initials: G
authors.lastname: Stimac
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Bannerman
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Roy
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Fokion
authors.initials: F
authors.lastname: Glykofrydis
authors.affiliation: School of Engineering, James Watt Building, University of Glasgow, GL12 8QQ, UK.
authors.forename: Huabing
authors.initials: H
authors.lastname: Yin
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XB, UK.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Davies
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D025461:Feedback, Physiological / Q000502:physiology*
keywords: autocrine secretion; branching morphogenesis; cell motility; positive feedback; self-organisation; shape