A distinction that rewards a promising and already fruitful scientific career.

Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. These events involve the remodeling of cell contacts driven by active cytoskeletal contractile forces. However how cell-cell contacts remodel remains poorly understood because of lack of tools to directly apply forces at cell-cell contacts to produce their remodeling. Here we develop a dual-optical trap manipulation method to impose different force patterns on cell-cell contacts in the early epithelium of the Drosophila embryo. Through different push and pull manipulations at the edges of junctions, the technique allows us to produce junction extension and junction shrinkage. We use these observations to constrain and specify vertex-based models of tissue mechanics, incorporating negative and positive mechanosensitive feedback depending on the type of remodeling. We show that Myosin-II activity responds to junction strain rate and facilitates full junction shrinkage. Altogether our work provides insight into how stress produces efficient deformation of cell-cell contacts in vivo and identifies unanticipated mechanosensitive features of their remodeling. Significance statement The highly organized tissues and organs that form our body emerge from internal dynamic activities at the cellular level. Among such activities, cell shape changes and cell rearrangement, cell extrusion and cell division sculpt epithelial tissues into elongated sheets, tubes and spherical cavities. Remodeling of cell-cell contacts, powered by actomyosin contractility, is key to all these transformations. Although much is known about the molecular machinery and biochemical signals that regulate remodeling of cell contacts, there is a lack of approaches to directly probe the mechanics of cell contacts and therefore assess their ability to resist or deform in response to mechanical loads. We developed an experimental technique to manipulate and exert contractile and extensile forces to cell-cell junctions. Our results lead to a specific physical model of junctional mechanics, with implications in the modeling of collective cell behavior in epithelial tissues. ### Competing Interest Statement The authors have declared no competing interest.

A cellular and biophysical study on embryonic stem cell aggregates reveals that the endoderm can form by a three-step mechanism involving a Wnt/beta-catenin-mediated epiblast fragmentation, tissue flow and cell segregation.

Roadmap for the multiscale coupling of biochemical and mechanical signals during development, Pierre-François Lenne, Edwin Munro, Idse Heemskerk, Aryeh Warmflash, Laura Bocanegra-Moreno, Kasumi Kishi, Anna Kicheva, Yuchen Long, Antoine Fruleux, Arezki Boudaoud, Timothy E Saunders, Paolo Caldarelli, Arthur Michaut, Jerome Gros, Yonit Maroudas-Sacks, Kinneret Keren, Edouard Hannezo, Zev J Gartner, Benjamin Stormo, Amy Gladfelter, Alan Rodrigues, Amy Shyer, Nicolas Minc, Jean-Léon Maître, Stefano Di Talia, Bassma Khamaisi, David Sprinzak, Sham Tlili

Cell-cell adhesion is more than the sum of its molecular parts. In this perspective, Lenne, Rupprecht, and Viasnoff aim at bridging scales from adhesion molecules and actomyosin networks to junctional integrity and mechanical resistance of tissues and organs.

Epithelial tissues acquire their integrity and function through the apico-basal polarization of their constituent cells. Proteins of the PAR and Crumbs complexes are pivotal to epithelial polarization, but the mechanistic understanding of polarization is challenging to reach, largely because numerous potential interactions between these proteins and others have been found, without clear hierarchy in importance. We identify the regionalized and segregated organization of members of the PAR and Crumbs complexes at epithelial apical junctions by imaging endogenous proteins using STED microscopy on Caco-2 cells, human and murine intestinal samples. Proteins organize in submicrometric clusters, with PAR3 overlapping with the tight junction (TJ) while PALS1-PATJ and aPKC-PAR6β form segregated clusters that are apical of the TJ and present in an alternated pattern related to actin organization. CRB3A is also apical of the TJ and weakly overlaps with other polarity proteins. This organization at the nanoscale level significantly simplifies our view on how polarity proteins could cooperate to drive and maintain cell polarity. ### Competing Interest Statement The authors have declared no competing interest.

Shaping the animal body plan is a complex process that involves the spatial organization and patterning of different layers of cells. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned group of cells into structured territories is largely unknown. Here, using 3D aggregates of mouse embryonic stem cells, we study the formation of one of the three germ layers, the endoderm. We show that the endoderm can be generated from an epiblast-like state by a three-tier mechanism: a release of islands of E-cadherin expressing cells, their flow toward the tip of the 3D aggregate, and their segregation. In contrast to the prevailing view, this mechanism does not require epithelial to mesenchymal transitions and vice-versa but rather a fragmentation, which is mediated by Wnt/β- catenin, and a sorting process. Our data emphasize the role of signaling and cell flows in the establishment of the body plan. ### Competing Interest Statement The authors have declared no competing interest.

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