Biophysics of organoids

In this review, Weichselberger, Moore et al. discuss how physics-based approaches illuminate organoid development and homeostasis by integrating mechanical, chemical, and informational processes. They...

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Sham Tlili, winner of the CNRS 2025 bronze medal - IBDM | Institut de Biologie du Développement de Marseille

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

ibdm.univ-amu.fr

Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo

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.

biorxiv.org

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

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.

doi.org

Roadmap for the multiscale coupling of biochemical and mechanical signals during development - IOPscience

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

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Cell Junction Mechanics beyond the Bounds of Adhesion and Tension

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.

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Super-resolution imaging uncovers the nanoscopic segregation of polarity proteins in epithelia

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.

biorxiv.org

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

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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Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

Tissue remodeling during embryogenesis is driven by the apical contractility of the epithelial cell cortex. This behavior arises notably from Rho1/Rok induced transient accumulation of non-muscle myosin II (MyoII pulses) pulling on actin filaments (F-Actin) of the medio-apical cortex. While recent studies begin to highlight the mechanisms governing the emergence of Rho1/Rok/MyoII pulsatility in different organisms, little is known about how the F-Actin organization influences this process. Focusing on Drosophila ectodermal cells during germband extension and amnioserosa cells during dorsal closure, we show that the medio-apical actomyosin cortex consists of two entangled F-Actin subpopulations. One exhibits pulsatile dynamics of actin polymerization in a Rho1 dependent manner. The other forms a persistent and homogeneous network independent of Rho1. We identify the Frl/Fmnl formin as a critical nucleator of the persistent network since modulating its level, in mutants or by overexpression, decreases or increases the network density. Absence of this network yields sparse connectivity affecting the homogeneous force transmission to the cell boundaries. This reduces the propagation range of contractile forces and results in tissue scale morphogenetic defects. Our work sheds new lights on how the F-Actin cortex offers multiple levels of regulation to affect epithelial cells dynamics.

biorxiv.org

Spatiotemporal dynamics of calcium transients during embryogenesis of Drosophila melanogaster

Calcium signaling plays a crucial role in the physiology of the organs but also in various aspects of the organogenesis of the embryo. High versatility of calcium signaling is encoded by the dynamic variation of intracellular calcium concentration. While the dynamics of calcium is important, little is known about it throughout the embryogenesis of the largest class of animals, insects. Here, we visualize calcium dynamics throughout embryogenesis of Drosophila using a fluorescent protein-based calcium indicator, GCaMP3, and report calcium transients in epithelium and neuronal tissues. Local calcium transients of varying duration were detected in the outer epithelium, trachea and neural cells. In addition, gap-junction-dependent calcium waves were identified at stage 16 in the outer epithelium and in the trachea at stage 17. Calcium transient waveform analysis revealed different characteristics as a function of the duration, location and frequency. Detailed characterization of calcium transients during embryogenesis of Drosophila will help us better understand the role of calcium signaling in embryogenesis and organogenesis of insects.

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