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Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis.

Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.

Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time play a central role in cell-cell contact formation and maturation. Yet, how this process is mechanistically achieved remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical Actin flows, driven by the depletion of Myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of Myosin-2 and a decrease of F-actin at the contact center. This depletion of Myosin-2 causes centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determine the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells.

Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization.

Epithelial barrier function is commonly analyzed using transepithelial electrical resistance (TER), which measures the ion flux across epithelia, or by adding traceable macromolecules to one side of the epithelium and monitoring their passage to the other side. While these methods effectively measure changes to global barrier function, they are not sensitive enough to detect local or transient disruptions in the barrier, and they do not reveal the location of barrier breaches within the context of cell or tissue morphology. Therefore, we developed a method that we named Zinc-based Ultrasensitive Microscopic Barrier Assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction (TJ) leaks with high spatial and temporal resolution (Stephenson et al., 2019; Varadarajan et al., 2021). Here, we present expanded applications for ZnUMBA. First, we show that ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin dynamics following laser injury of the junction. We also demonstrate that ZnUMBA can be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin-Darby Canine Kidney II (MDCK II) epithelial cells. ZnUMBA is a powerful and flexible method that, with some optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision.

Dynamic reorganization of the cytoplasm is key to many core cellular processes, such as cell division, cell migration and cell polarization. Cytoskeletal rearrangements are thought to constitute the main drivers of cytoplasmic flows and reorganization. In contrast, remarkably little is known about how dynamic changes in size and shape of cell organelles affect large-scale cytoplasmic organization. Here, we show that within the maturing zebrafish oocyte, the surface localization of exocytosis-competent cortical granules upon germinal vesicle breakdown is achieved by the combined activities of yolk granule fusion and microtubule aster formation and translocation. We find that cortical granules are moved towards the oocyte surface through radially-outward cytoplasmic flows induced by yolk granules fusing within the oocyte center in response to GV breakdown. We further show that vesicles decorated with the small Rab GTPase Rab11, a master regulator of vesicular trafficking and exocytosis, accumulate together with cortical granules at the oocyte surface. This accumulation is achieved by Rab11-positive vesicles being transported by acentrosomal microtubule asters, the formation of which is induced by the release of CyclinB/Cdk1 upon GV breakdown, and which display a net movement towards the oocyte surface by preferentially binding to the oocyte actin cortex. We finally demonstrate that the decoration of cortical granules by Rab11 at the oocyte surface is needed for cortical granule release and subsequent chorion elevation, a process central in oocyte activation. Collectively, these findings unravel a yet unrecognized role of organelle fusion, functioning together with cytoskeletal rearrangements, in determining cytoplasmic organization during oocyte maturation.

Convergence of paradigms yields patterns In embryo development, spatial patterns of distinct cell types arise reproducibly. In the zebrafish spinal cord, neural progenitors form stereotypic stripe patterns despite the noisy instructive signals and large-scale cellular rearrangement required during morphogenesis. Tsai et al. show that a cell type–specific adhesion code, regulated by a Shh morphogen gradient composed of three adhesion molecules, provides adhesion specificity for three neural progenitor types and mediates patterning robustness in the zebrafish spinal cord. Although insufficient on their own, the integration of the morphogen gradient and differential adhesion mechanisms enables robust pattern formation during tissue morphogenesis. Science , this issue p. 113

Significance Cell–cell contact formation is a key step in the evolution of multicellularity. While the molecular and cellular processes underlying cell–cell adhesion and contact formation have been extensively studied, comparably little is known about the physical principles guiding these processes. Actomyosin cortex tension differentially applied at the cell–cell and cell–medium interfaces was shown to promote expansion of the cell–cell contacts. Here, we uncover a nonlinear relationship between cortex tension and cell–cell contact size; in a low-tension regime, cell–cell contact size positively scales with cortex tension, while the high-tension regime promotes small contacts. This change in behavior is due to tension decreasing the turnover of adhesion molecules at the cell–cell contact, limiting contact expansion.

Intercellular adhesion is the key to multicellularity, and its malfunction plays an important role in various developmental and disease-related processes. Although it has been intensively studied by both biologists and physicists, a commonly accepted definition of cell-cell adhesion is still being debated. Cell-cell adhesion has been described at the molecular scale as a function of adhesion receptors controlling binding affinity, at the cellular scale as resistance to detachment forces or modulation of surface tension, and at the tissue scale as a regulator of cellular rearrangements and morphogenesis. In this review, we aim to summarize and discuss recent advances in the molecular, cellular, and theoretical description of cell-cell adhesion, ranging from biomimetic models to the complexity of cells and tissues in an organismal context. In particular, we will focus on cadherin-mediated cell-cell adhesion and the role of adhesion signaling and mechanosensation therein, two processes central for understanding the biological and physical basis of cell-cell adhesion.

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant., Activation of the zygotic genome is a critical transition during development, though the link to tissue-specific gene regulation remains unclear. Here the authors demonstrate distinct functions for Satb2 before and after zygotic genome activation, highlighting the temporal coordination of these roles.

Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.

The transient but pronounced ventral tail bending is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape (Lu et al., 2020). Here, we identify one key upstream regulator of ventral tail bending in the ascidian Ciona embryo. We show that during early tailbud stage, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin (pMLC) accumulated. We further show that interfering with the function of the BMP ligand Admp leads to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using a ultraviolet laser relaxes ventral tail bending. Based on these results, we propose a novel function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.Summary StatementAdmp is an upstream regulator of tail bending in the chordate Ciona tailbud embryo, determining tissue polarity of the ventral midline epidermis by localizing phosphorylated myosin.

Although rigidity and jamming transitions have been widely studied in physics and material science, their importance in a number of biological processes, including embryo development, tissue homeostasis, wound healing, and disease progression, has only begun to be recognized in the past few years. The hypothesis that biological systems can undergo rigidity/jamming transitions is attractive, as it would allow these systems to change their material properties rapidly and strongly. However, whether such transitions indeed occur in biological systems, how they are being regulated, and what their physiological relevance might be, is still being debated. Here, we review theoretical and experimental advances from the past few years, focussing on the regulation and role of potential tissue rigidity transitions in different biological processes.

Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future.

The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.Impact StatementIncomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site.

Lymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.

Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s).Graphical abstractHighlightSpindle tilting in anisotropic cell shape induces unequal cell divisionCortical polarity domain can exert attractive or repulsive effect on spindleCell geometry and polarity domain cooperate to position the spindleCell geometry modulates the effect of polarity domain

Tissue morphogenesis is driven by mechanical forces triggering cell movements and shape changes. Quantitatively measuring tension within tissues is of great importance for understanding the role of mechanical signals acting on the cell and tissue level during morphogenesis. Here we introduce laser ablation as a useful tool to probe tissue tension within the granulosa layer, an epithelial monolayer of somatic cells that surround the zebrafish female gamete during folliculogenesis. We describe in detail how to isolate follicles, mount samples, perform laser surgery, and analyze the data.

Summary Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context., Graphical abstract, Highlights • Zebrafish morphogenesis starts with a tissue rigidity phase transition • Percolation theory predicts this transition based on the cell connectivity network • Cell-cell adhesion defines the cell connectivity network and thus tissue rigidity • Cell-cycle synchrony ensures a uniform transition by randomly changing connectivity, A general theoretical approach, rooted in cell connectivity, enables prediction of phase transitions at the tissue scale.

Tissue morphogenesis is driven by mechanical forces triggering cell movements and shape changes. Quantitatively measuring tension within tissues is of great importance for understanding the role of mechanical signals acting on the cell and tissue level during morphogenesis. Here we introduce laser ablation as a useful tool to probe tissue tension within the granulosa layer, an epithelial monolayer of somatic cells that surround the zebrafish female gamete during folliculogenesis. We describe in detail how to isolate follicles, mount samples, perform laser surgery, and analyze the data.

Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.

Cytoplasm is a gel-like crowded environment composed of various macromolecules, organelles, cytoskeletal networks, and cytosol. The structure of the cytoplasm is highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules are restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the crowded nature of the cytoplasm at the microscopic scale, large-scale reorganization of the cytoplasm is essential for important cellular functions, such as cell division and polarization. How such mesoscale reorganization of the cytoplasm is achieved, especially for large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, is only beginning to be understood. In this review, we will discuss recent advances in elucidating the molecular, cellular, and biophysical mechanisms by which the cytoskeleton drives cytoplasmic reorganization across different scales, structures, and species.

Global tissue tension anisotropy has been shown to trigger stereotypical cell division orientation by elongating mitotic cells along the main tension axis. Yet, how tissue tension elongates mitotic cells despite those cells undergoing mitotic rounding (MR) by globally upregulating cortical actomyosin tension remains unclear. We addressed this question by taking advantage of ascidian embryos, consisting of a small number of interphasic and mitotic blastomeres and displaying an invariant division pattern. We found that blastomeres undergo MR by locally relaxing cortical tension at their apex, thereby allowing extrinsic pulling forces from neighboring interphasic blastomeres to polarize their shape and thus division orientation. Consistently, interfering with extrinsic forces by reducing the contractility of interphasic blastomeres or disrupting the establishment of asynchronous mitotic domains leads to aberrant mitotic cell division orientations. Thus, apical relaxation during MR constitutes a key mechanism by which tissue tension anisotropy controls stereotypical cell division orientation.

Epiboly is a conserved gastrulation movement describing the thinning and spreading of a sheet or multi-layer of cells. The zebrafish embryo has emerged as a vital model system to address the cellular and molecular mechanisms that drive epiboly. In the zebrafish embryo, the blastoderm, consisting of a simple squamous epithelium (the enveloping layer) and an underlying mass of deep cells, as well as a yolk nuclear syncytium (the yolk syncytial layer) undergo epiboly to internalize the yolk cell during gastrulation. The major events during zebrafish epiboly are: expansion of the enveloping layer and the internal yolk syncytial layer, reduction and removal of the yolk membrane ahead of the advancing blastoderm margin and deep cell rearrangements between the enveloping layer and yolk syncytial layer to thin the blastoderm. Here, work addressing the cellular and molecular mechanisms as well as the sources of the mechanical forces that underlie these events is reviewed. The contribution of recent findings to the current model of epiboly as well as open questions and future prospects are also discussed.

Gastrulation entails specification and formation of three embryonic germ layers-ectoderm, mesoderm and endoderm-thereby establishing the basis for the future body plan. In zebrafish embryos, germ layer specification occurs during blastula and early gastrula stages (Ho & Kimmel, 1993), a period when the main morphogenetic movements underlying gastrulation are initiated. Hence, the signals driving progenitor cell fate specification, such as Nodal ligands from the TGF-β family, also play key roles in regulating germ layer progenitor cell segregation (Carmany-Rampey & Schier, 2001; David & Rosa, 2001; Feldman et al., 2000; Gritsman et al., 1999; Keller et al., 2008). In this review, we summarize and discuss the main signaling pathways involved in germ layer progenitor cell fate specification and segregation, specifically focusing on recent advances in understanding the interplay between mesoderm and endoderm specification and the internalization movements at the onset of zebrafish gastrulation.

Epiboly is a conserved gastrulation movement describing the thinning and spreading of a sheet or multi-layer of cells. The zebrafish embryo has emerged as a vital model system to address the cellular and molecular mechanisms that drive epiboly. In the zebrafish embryo, the blastoderm, consisting of a simple squamous epithelium (the enveloping layer) and an underlying mass of deep cells, as well as a yolk nuclear syncytium (the yolk syncytial layer) undergo epiboly to internalize the yolk cell during gastrulation. The major events during zebrafish epiboly are: expansion of the enveloping layer and the internal yolk syncytial layer, reduction and removal of the yolk membrane ahead of the advancing blastoderm margin and deep cell rearrangements between the enveloping layer and yolk syncytial layer to thin the blastoderm. Here, work addressing the cellular and molecular mechanisms as well as the sources of the mechanical forces that underlie these events is reviewed. The contribution of recent findings to the current model of epiboly as well as open questions and future prospects are also discussed.

Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water...

Summary During animal development, cell-fate-specific changes in gene expression can modify the material properties of a tissue and drive tissue morphogenesis. While mechanistic insights into the genetic control of tissue-shaping events are beginning to emerge, how tissue morphogenesis and mechanics can reciprocally impact cell-fate specification remains relatively unexplored. Here we review recent findings reporting how multicellular morphogenetic events and their underlying mechanical forces can feed back into gene regulatory pathways to specify cell fate. We further discuss emerging techniques that allow for the direct measurement and manipulation of mechanical signals in vivo , offering unprecedented access to study mechanotransduction during development. Examination of the mechanical control of cell fate during tissue morphogenesis will pave the way to an integrated understanding of the design principles that underlie robust tissue patterning in embryonic development.

Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book 'On Growth and Form' has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology.

The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.

Intra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed., It is unknown how endocardium growth is coordinated with that of the myocardium in the zebrafish. Here, the authors show that myocardial chamber volume expansion causes increased endocardial tissue tension, which in turn triggers Hippo signaling-mediated proliferation within the endocardium.