Multicellular dynamics during epithelial elongation.

Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Seminars in Cell and Developmental Biology (Impact Factor: 5.97). 07/2008; 19(3):263-70. DOI: 10.1016/j.semcdb.2008.01.005
Source: PubMed

ABSTRACT The reorganization of multicellular populations to produce an elongated tissue structure is a conserved mechanism for shaping the body axis and several organ systems. In the Drosophila germband epithelium, this process is accompanied by the formation of a planar polarized network of junctional and cytoskeletal proteins in response to striped patterns of gene expression. Actomyosin cables and adherens junctions are dynamically remodeled during intercalation, providing the basis for polarized cell behavior. Quantitative analysis of cell behavior in living embryos reveals unexpected cell population dynamics that include the formation of multicellular rosette structures as well as local neighbor exchange.

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    ABSTRACT: E-cadherin belongs to the classic cadherin subfamily of calcium-dependent cell adhesion molecules and is crucial for the formation and function of epithelial adherens junctions. In this study, we demonstrate that Vangl2, a vertebrate regulator of planar cell polarity (PCP), controls E-cadherin in epithelial cells. E-cadherin co-immunoprecipitates with Vangl2 from embryonic kidney extracts, and this association is also observed in transfected fibroblasts. Vangl2 enhances the internalization of E-cadherin when overexpressed. Conversely, the quantitative ratio of E-cadherin exposed to the cell surface is increased in cultured renal epithelial cells derived from Vangl2(Lpt/+) mutant mice. Interestingly, Vangl2 is also internalized through protein traffic involving Rab5- and Dynamin-dependent endocytosis. Taken together with recent reports regarding the transport of Frizzled3, MMP14 and nephrin, these results suggest that one of the molecular functions of Vangl2 is to enhance the internalization of specific plasma membrane proteins with broad selectivity. This function may be involved in the control of intercellular PCP signalling or in the PCP-related rearrangement of cell adhesions.
    Scientific Reports 11/2014; 4:6940. DOI:10.1038/srep06940 · 5.08 Impact Factor
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    ABSTRACT: Cells are linked together dynamically by adhesion molecules, such as the classical cadherins. E-cadherin, which mediates epithelial cell–cell interactions, plays fundamental roles in tissue organization and is often perturbed in diseases such as cancer. It has long been recognized that the biology of E-cadherin arises from cooperation between adhesion and the actin cytoskeleton. A major feature is the generation of contractile forces at junctions, yielding patterns of tension that contribute to tissue integrity and patterning. Here we discuss recent developments in understanding how cadherin junctions integrate signaling and cytoskeletal dynamics to sense and generate force.
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    ABSTRACT: Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division, cell rearrangements, and changes in cell shape. Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalations around the tubule circumference, producing convergent-extension tissue movements. Using genetic techniques, we demonstrate that the vector of cell movement is regulated by localised epidermal growth factor (EGF) signalling from the distally placed tip cell lineage, which sets up a distal-to-proximal gradient of pathway activation to planar polarise cells, without the involvement for PCP gene activity. Time-lapse imaging at subcellular resolution shows that the acquisition of planar polarity leads to asymmetric pulsatile Myosin II accumulation in the basal, proximal cortex of tubule cells, resulting in repeated, transient shortening of their circumferential length. This repeated bias in the polarity of cell contraction allows cells to move relative to each other, leading to a reduction in cell number around the lumen and an increase in tubule length. Physiological analysis demonstrates that animals whose tubules fail to elongate exhibit abnormal excretory function, defective osmoregulation, and lethality.
    PLoS Biology 12/2014; 12(12):e1002013. DOI:10.1371/journal.pbio.1002013 · 11.77 Impact Factor


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