Highlights d Caveolae influence contractile tension in epithelial monolayers d Caveolin-1 depletion enhances epithelial tension via PtdIns(4,5)P 2 signaling d Elevated epithelial tension inhibits oncogenic cell extrusion

Highlights d Shootin1a couples F-actin retrograde flow and cell adhesions in dendritic spines d Synaptic activation enhances shootin1a-mediated clutch coupling in spines d Shootin1a-mediated clutch coupling generates force for spine formation d Activity-induced spine enlargement requires shootin1amediated clutch coupling

By happy chance, the founding of Traffic in 1999 coincided with a clutch of reports that documented the endocytosis and recycling of classical cadherin adhesion receptors. This stimulated a concerted effort to elucidate the molecular regulation of cadherin endocytosis and to identify its functional implications. In particular, endocytosis provided new perspectives to understand how cadherins are modulated during tissue morphogenesis. In this short article, we consider some of what we have learnt about this problem and identify open questions for future research.

Background Information Epithelial collective cell migration requires the intrinsic locomotor activity of cells to be coordinated across populations. This coordination is governed by the presence of cell–cell adhesions as well as the cooperative behaviour of cells within the monolayer. Results Here, we report a role for Caveolin‐1 (CAV1) in epithelial collective cell migration. CAV1 depletion reduced the migratory behaviour of AML12 liver epithelial cells when grown as monolayers, but not as individual cells. This suggested that CAV1 is a component of the process by which multicellular collectivity regulates epithelial motility. The correlation length for migration velocity was increased by CAV1 RNAi, a possible sign of epithelial jamming. However, CAV1 RNAi reduced migration, even when monolayers were allowed to migrate into unconfined spaces. The migratory defect was ameliorated by simultaneous depletion of the FMNL2 formin, whose cortical recruitment is increased in CAV1 RNAi cells. Conclusions We therefore suggest that CAV1 modulates intraepithelial motility by controlling the cortical availability of FMNL2. Significance Although epithelial collective cell migration has been observed in multiple contexts both in vivo and in vitro, the inherent coupling and coordination of activity between cells within the monolayer remain incompletely understood. Our study highlights a role for CAV1 in regulating intraepithelial motility, an effect that involves the formin FMNL2.

Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required b1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.