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


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 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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Figure 1: Morphology and cellular dynamics during dorsal fold formation.
Figure 2: The dynamics of Bazooka and Par-1 during dorsal fold initiation.
Figure 3: Differential positioning of adherens junctions is necessary and overexpression of Bazooka can be sufficient for ectopic dorsal fold initiation.
Figure 4: Loss of aPKC results in an expansion of the junctional domain and a failure to shorten the initiating cells.


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We thank A. Martin, J. McDonald, D. St Johnston and J. Zallen for providing flies and antibodies; J. Goodhouse and S. Thiberge for assistance in microscopy; G. Deshpande, members of the Wieschaus and Schüpbach laboratories for helpful comments on the manuscript and discussion. This work is supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation to Y.-C.W., a National Institutes of Health/National Institute of General Medical Sciences P50 grant (GM071508) to Z.K. and M.K., and a National Institute of Child Health and Human Development grant (5R37HD15587) to E.F.W. E.F.W. is an investigator of the Howard Hughes Medical Institute.

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Y.-C.W. conceived the project, performed all experiments and analysed the data, except those experiments that involve scanning electron microscopy, which were performed by E.F.W.; Z.K. and M.K. developed the software for three-dimensional reconstruction. Y.-C.W. and E.F.W. wrote the manuscript.

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Correspondence to Eric F. Wieschaus.

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Wang, YC., Khan, Z., Kaschube, M. et al. Differential positioning of adherens junctions is associated with initiation of epithelial folding. Nature 484, 390–393 (2012).

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