Differential positioning of adherens junctions is associated with initation of epithelial folding

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Nature (Impact Factor: 41.46). 03/2012; 484(7394):390-3. DOI: 10.1038/nature10938
Source: PubMed


During tissue morphogenesis, simple epithelial sheets undergo folding to form complex structures. The prevailing model underlying epithelial folding involves cell shape changes driven by myosin-dependent apical constriction. Here we describe an alternative mechanism that requires differential positioning of adherens junctions controlled by modulation of epithelial apical-basal polarity. Using live embryo imaging, we show that before the initiation of dorsal transverse folds during Drosophila gastrulation, adherens junctions shift basally in the initiating cells, but maintain their original subapical positioning in the neighbouring cells. Junctional positioning in the dorsal epithelium depends on the polarity proteins Bazooka and Par-1. In particular, the basal shift that occurs in the initiating cells is associated with a progressive decrease in Par-1 levels. We show that uniform reduction of the activity of Bazooka or Par-1 results in uniform apical or lateral positioning of junctions and in each case dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par-1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions not only alters the apical shape of the initiating cells, but also forces the lateral membrane of the adjacent cells to bend towards the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.

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Available from: Eric Wieschaus, Sep 25, 2014
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    • "In most cases, however, the common mechanisms and forces involved in cellular shortening in different contexts are not clear. They could result from lateral actomyosin activity (Wu et al., 2014) or from changes in the length distribution of microtubules (Picone et al., 2010), or through the microtubule-dependent positioning of junctions (Wang et al., 2012). One system in which this process of shortening has been studied in most detail is the Drosophila egg chamber. "
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    • "Changing cell shape is a basic cellular behavior during dynamic tissue morphogenesis (Fristrom, 1988). Various morphogenetic events are known to coincide with cellular shape changes (Condic et al., 1991;Taniguchi et al., 2011;Wang et al., 2012), and a few reports suggest that regulation of apical cell shape is required for proper morphogenesis (Nelson et al., 2012;Taniguchi et al., 2011). Although the correlation between PCP signaling and polarized cellular geometries has been shown to be poor in flies (Aigouy et al., 2010;Bosveld et al., 2012), here we report that the geometric characteristics of the cellular apical surface are regulated by the PCP pathway in mouse oviduct epithelium. "
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    • "Adherens junction proteins move from their normal subapical localization to a more extreme apical localization in the VF cells just before apical constriction (Fig. 2E; Dawes-Hoang et al., 2007). We do not know how much influence their location along the apical-basal axis has on the ability of cells to invaginate in the VF, although adherens junction migration is known to be a driving force in Drosophila dorsal epithelial folding (Wang et al., 2012). The transmembrane protein Crumbs is also a major player in apical membrane identity and recruitment of proteins to the apical region of cells during later stages (Assémat et al., 2008). "
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