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.
View Article and Find Full Text PDFBackground 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.
Cellular traction forces influence epithelial behavior, including wound healing and cell extrusion. Here, we describe a simple traction force microscopy (TFM) protocol using ECM protein-coated polydimethylsiloxane substrate and widefield fluorescence microscopy. We include detailed steps for analysis so readers can obtain traction forces to study the mechanobiology of epithelial cells.
View Article and Find Full Text PDFEpithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell.
View Article and Find Full Text PDFCell extrusion is a striking morphological event found in epithelia and endothelia. It is distinguished by two symmetry-breaking events: a loss of planar symmetry, as cells are extruded in either apical or basal directions; and loss of mechanochemical homogeneity within monolayers, as cells that are fated to be extruded become biochemically and mechanically distinct from their neighbors. Cell extrusion is elicited by many diverse events, from apoptosis to the expression of transforming oncogenes.
View Article and Find Full Text PDFEpithelia are active materials where mechanical tension governs morphogenesis and homeostasis. But how that tension is regulated remains incompletely understood. We now report that caveolae control epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion.
View Article and Find Full Text PDFBiochem Soc Trans
August 2019
Classical cadherin cell adhesion receptors are integral membrane proteins that mediate cell-cell interactions, tissue integrity and morphogenesis. Cadherins are best understood to function as membrane-spanning molecular composites that couple adhesion to the cytoskeleton. On the other hand, the membrane lipid environment of the cadherins is an under-investigated aspect of their cell biology.
View Article and Find Full Text PDFHost-protective caspase-1 activity must be tightly regulated to prevent pathology, but mechanisms controlling the duration of cellular caspase-1 activity are unknown. Caspase-1 is activated on inflammasomes, signaling platforms that facilitate caspase-1 dimerization and autoprocessing. Previous studies with recombinant protein identified a caspase-1 tetramer composed of two p20 and two p10 subunits (p20/p10) as an active species.
View Article and Find Full Text PDFRho kinases (ROCK1 and ROCK2) function downstream of the small GTPase RhoA to drive actomyosin cytoskeletal remodeling. It has often been believed that ROCK1 and ROCK2 may be functionally redundant, as they share a highly conserved kinase domain. However, in this study, we report differential functional effects for these ROCKs at the epithelial zonula adherens (ZA).
View Article and Find Full Text PDFCell contractility, driven by the RhoA GTPase, is a fundamental determinant of tissue morphogenesis. In this issue, Mason et al. (2016.
View Article and Find Full Text PDFCell migration and spreading is driven by actin polymerization and actin stress fibers. Actin stress fibers are considered to contain α-actinin crosslinkers and nonmuscle myosin II motors. Although several actin stress fiber subtypes have been identified in migrating and spreading cells, the degree of molecular diversity of their composition and the signaling pathways regulating fiber subtypes remain largely uncharacterized.
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