Early autonomous patterning of the anteroposterior axis in gastruloids.

Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates - such as gastruloids - can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood.

Regulation of intercellular viscosity by E-cadherin-dependent phosphorylation of EGFR in collective cell migration.

Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role in regulating cell cohesion and migration dynamics during tissue remodeling. While the role and origin of the junctional mechanical tension at AJs have been extensively studied, the influence of the actin cortex structure and dynamics on junction plasticity remains incompletely understood.

The positioning mechanics of microtubule asters in embryo explants.

Microtubule asters are essential in localizing the action of microtubules in processes including mitosis and organelle positioning. In large cells, such as the one-cell sea urchin embryo, aster dynamics are dominated by hydrodynamic pulling forces. However, in systems with more densely positioned nuclei such as the early embryo, which packs around 6000 nuclei within the syncytium in a crystalline-like order, it is unclear what processes dominate aster dynamics.

Learning the mechanobiology of development from gastruloids.

Gastruloids acquire their organization and shape through cell biochemical and mechanical activities. Such activities determine the physical forces and changes in material properties that transform simple spherical aggregates into organized tissues. In this Perspective, we discuss why the concepts and approaches of mechanobiology, a discipline that focuses on cell and tissue mechanics and its contribution to the organization and functions of living systems, are essential to the gastruloid field and, in turn, what gastruloids may teach us about mechanobiology.

A microfluidic platform to investigate the role of mechanical constraints on tissue reorganization.

Mechanical constraints have a high impact on development processes, and there is a need for new tools to investigate the role of mechanosensitive pathways in tissue reorganization during development. We present here experiments in which embryonic cell aggregates are aspired through constrictions in microfluidic channels, generating highly heterogeneous flows and large cell deformations that can be imaged using two-photon microscopy. This approach provides a way to measure in situ local viscoelastic properties of 3D tissues and connect them to intracellular and intercellular events, such as cell shape changes and cell rearrangements.

Condensation of the Drosophila nerve cord is oscillatory and depends on coordinated mechanical interactions.

During development, organs reach precise shapes and sizes. Organ morphology is not always obtained through growth; a classic counterexample is the condensation of the nervous system during Drosophila embryogenesis. The mechanics underlying such condensation remain poorly understood.

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 the different germ layers. 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 cell ensemble into structured territories is largely unknown. Here, using gastruloids -3D aggregates of mouse embryonic stem cells- we study the formation of one of the three germ layers, the endoderm.

Aster repulsion drives short-ranged ordering in the Drosophila syncytial blastoderm.

Biological systems are highly complex, yet notably ordered structures can emerge. During syncytial stage development of the Drosophila melanogaster embryo, nuclei synchronously divide for nine cycles within a single cell, after which most of the nuclei reach the cell cortex. The arrival of nuclei at the cortex occurs with remarkable positional order, which is important for subsequent cellularisation and morphological transformations.

Amoeboid Swimming Is Propelled by Molecular Paddling in Lymphocytes.

Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like crawling of fibroblasts, relies on maturation of adhesion complexes and actin fiber traction, whereas the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on two-dimensional and in three-dimensional solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming.

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish.

The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation.

Activation of butterfly eyespots by Distal-less is consistent with a reaction-diffusion process.

Eyespots on the wings of nymphalid butterflies represent colorful examples of pattern formation, yet the developmental origins and mechanisms underlying eyespot center differentiation are still poorly understood. Using CRISPR-Cas9 we re-examine the function of Distal-less (Dll) as an activator or repressor of eyespots, a topic that remains controversial. We show that the phenotypic outcome of CRISPR mutations depends upon which specific exon is targeted.

Influence of proliferation on the motions of epithelial monolayers invading adherent strips.

Biological systems integrate dynamics at many scales, from molecules, protein complexes and genes, to cells, tissues and organisms. At every step of the way, mechanics, biochemistry and genetics offer complementary approaches to understand these dynamics. At the tissue scale, in vitro monolayers of epithelial cells provide a model to capture the influence of various factors on the motions of the tissue, in order to understand in vivo processes from morphogenesis, cancer progression and tissue remodelling.

Collective cell migration without proliferation: density determines cell velocity and wave velocity.

Collective cell migration contributes to embryogenesis, wound healing and tumour metastasis. Cell monolayer migration experiments help in understanding what determines the movement of cells far from the leading edge. Inhibiting cell proliferation limits cell density increase and prevents jamming; we observe long-duration migration and quantify space-time characteristics of the velocity profile over large length scales and time scales.

Colloquium: Mechanical formalisms for tissue dynamics.

The understanding of morphogenesis in living organisms has been renewed by tremendous progress in experimental techniques that provide access to cell scale, quantitative information both on the shapes of cells within tissues and on the genes being expressed. This information suggests that our understanding of the respective contributions of gene expression and mechanics, and of their crucial entanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assist the design and interpretation of experiments, point out the main ingredients and assumptions, and ultimately lead to predictions.

Multicellular aggregates: a model system for tissue rheology.

Morphogenetic processes involve cell flows. The mechanical response of a tissue to active forces is linked to its effective viscosity. In order to decouple this mechanical response from the complex genetic changes occurring in a developing organism, we perform rheometry experiments on multicellular aggregates, which are good models for tissues.

Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway.

During animal development, several planar cell polarity (PCP) pathways control tissue shape by coordinating collective cell behavior. Here, we characterize by means of multiscale imaging epithelium morphogenesis in the Drosophila dorsal thorax and show how the Fat/Dachsous/Four-jointed PCP pathway controls morphogenesis. We found that the proto-cadherin Dachsous is polarized within a domain of its tissue-wide expression gradient.