PgmNr D1018: Tension-dependent junction remodeling repositions polarity proteins and coordinates EMT progression.

Authors:
M. Weng 1,2 ; E. Wieschaus 1,2


Institutes
1) Princeton University, Princeton, NJ; 2) The Howard Hughes Medical Institute.


Keyword: cell polarity

Abstract:

Although Snail (Sna) is the driving factor of epithelial-mesenchymal-transition (EMT), loss of adherens junctions and polarity in Drosophila gastrula is delayed until mesoderm is internalized, despite the early expression of Sna in that primordium. By combining live imaging and quantitative image analysis, we show that contractile myosin on the apical surface of the epithelia that triggers the internalization of the tissue, also strengthens and repositions the adherens junctions, which in turn repositions and delays the complete loss of the polarity proteins until the completion of tissue morphogenesis. We found that before the initiation of mesoderm internalization, expression of Sna in mesodermal epithelia leads to a series of changes that resembles partial EMT: decreased localization of polarity proteins such as Bazooka (Baz) and aPKC, downregulation of cortical actin, and disassembly of adherens junctions. Similar phenotypes can be induced by ectopic expression of Sna in ectoderm. Such Snail-dependent junction loss appears to be mediated by loss of Baz, as Baz knockdown leads to a similar loss of adherens junctions whereas Baz localization maintains in the absence of junctions. The decrease in junction level however is reversed upon the activation of apical myosin despite the continued Sna expression. Adherens junctions then are shifted from subapical position to apical position and strengthened in a myosin-dependent manner. Although Baz is not recovered as much as the junctions and results in decreased ratio between Baz and junctions, its level is maintained until tissue internalization. By tracking individual junction and Baz clusters, we found that as the junction clusters shift apically, Baz is often left behind to diminish but is quickly restored in the newly positioned junction clusters. This junction-directed polarity redistribution can override the polarity protein redistribution mechanism that drives basal junction shift during dorsal folds formation, as ectopic activation of myosin in those cells can induce apical repositioning of junctions and Baz and abolishes the dorsal folds. In summary, to prepare timely EMT of mesodermal tissue early expression of Snail induces partial EMT meanwhile to ensure proper folding of the tissue preceding EMT, the contractile actomyosin, the same machinery that drives the morphogenic event, is used to pause the partial EMT by reorganizing adherens junctions followed by the redistribution of polarity proteins.