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

Abstract

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 constriction1. 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 prior to 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 neighboring 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 toward the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.

Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct

“…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.…”

PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility

“…In the male reproductive tract, epithelial folding has only been observed in mouse efferent ducts after constitutive activation of NOTCH1 signaling (18) and has not been observed in other Pten knockout models. During normal tissue morphogenesis, epithelial folding is mediated by cell shape changes driven by apical constriction or, alternatively, by differential positioning of adherens junctions (19). Whether this process occurs in the initial segment after loss of Pten is unclear, but our data suggest that PTEN is a regulator of epithelial folding.…”

Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

“…Apical constriction by its definition is linked to apical-basal polarity, and changes in the activity of proteins that regulate apical-basal polarity can result in apical constriction, sometimes without an obvious increase in myosin activity (Rohrschneider and Nance, 2009;Fanning et al, 2012;Wang et al, 2012). Given the reduction of apical surface area, the removal of excess apical membrane could also play a crucial role in constriction (Lee and Harland, 2010;Mateus et al, 2011).…”