Abstract

Name: Marc Trani Bustos

Affiliation: Max Planck Institute for Cell Biology and Genetics, Dresden, Germany

Title: Building the mammalian embryo body: tissue surface mechanics constrains proliferation-driven forces to guide axial elongation.

Abstract: Mammalian embryos undergo complex morphogenetic changes after implantation in the uterus. The elongation of the body along a head-to-tail axis is a pivotal event, as it lays the foundation of the body plan. While genetic and biochemical aspects of mammalian body elongation have been uncovered, the physical mechanism of axial morphogenesis remains unknown, largely due to the inaccessibility of the implanted embryo to physical measurements and manipulations in utero. Gastruloids, a stem-cell-based embryo model of mammalian axial morphogenesis, lift such limitations. Combining live imaging, direct mechanical measurements, and chemical and mechanical perturbations, here we show that axis elongation in mouse and human gastruloids is guided by a posterior ‘actin cap’ at the tissue surface that constrains the expansive forces of cell proliferation. Measurements of mechanical stresses using oil microdroplets, as well as inhibition of cell proliferation and myosin activity, show that the forces driving elongation arise from cell proliferation, and not from convergent extension movements. We find that isotropic tissue expansion is re-directed into posterior elongation by the formation of a supracellular actin cap at the posterior tissue surface that restricts lateral tissue expansion. Finally, we show that posterior elongation in mouse embryos displays the key features of the physical elongation mechanism reported for mouse and human gastruloids. These findings reveal that mammalian body axis elongation, including human, occurs via a different physical mechanism from other vertebrate species.  

Preprint: https://doi.org/10.1101/2025.10.27.684710

Denis Krndija

Affiliation: Group Leader (ATIP-Avenir), Centre for Integrative Biology (CBI), Molecular, Cellular and Developmental Biology (MCD), France

Title: “Cracking” the Gut Epithelium: How Goblet Cells Mechanically Disrupt the Gut Barrier

Abstract: The intestinal epithelium, one of the largest epithelial surfaces, has to maintain a tight barrier against the harsh luminal environment. Barrier integrity primarily depends on cell-cell junctions formed by enterocytes, absorptive cells characterised by their polygonal and columnar morphology. In contrast, mucus-producing goblet cells, which are interspersed among enterocytes, exhibit a rounded apical cell shape and a voluminous body – raising the question of how epithelial integrity is maintained among cells with such different morphologies. Here, we show that goblet cells mechanically induce tight junction fractures between neighbouring enterocytes under homeostatic conditions in vivo, and that this effect is exacerbated during goblet cell hypertrophy, leading to increased gut permeability. Using a combination of in vivo (mouse) and organoid models, along with pharmacological, genetic and mechanical perturbations, as well as theoretical modelling, we demonstrate that these fractures arise from a force imbalance at cell interfaces: goblet cells exert compressive forces that deform adjacent enterocytes, whose junctions rupture depending on tissue rheology controlled by myosin II. Together, our findings uncover a previously unrecognised mechanical role of goblet cells in destabilising epithelial cohesion and establish cell type heterogeneity and intercellular force balance as critical determinants of junctional integrity and gut barrier function.