Publications

DISSECT is a tool to segment and explore cell and tissue mechanics in highly deformed 3D epithelia

Tatiana Merle*, Sophie Theis*, Alain Kamgoué, Emmanuel Martin, Florian Sarron, Guillaume Gay, Emmanuel Farge, Magali Suzanne

Developmental Cell, 2023, doi: 10.1016/j.devcel.2023.07.017

Understanding morphogenesis strongly relies on the characterization of tissue topology and mechanical properties deduced from imaging data. The development of new imaging techniques offers the possibility to go beyond the analysis of mostly flat surfaces and image and analyze complex tissue organization in depth. An important bottleneck in this field is the need to analyze imaging datasets and extract quantifications not only of cell and tissue morphology but also of the cytoskeletal network’s organization in an automatized way. Here, we describe a method, called DISSECT, for DisPerSE (Discrete Persistent Structure Extractor)-based Segmentation and Exploration of Cells and Tissues, that offers the opportunity to extract automatically, in strongly deformed epithelia, a precise characterization of the spatial organization of a given cytoskeletal network combined with morphological quantifications in highly remodeled three-dimensional (3D) epithelial tissues. We believe that this method, applied here to Drosophila tissues, will be of general interest in the expanding field of morphogenesis and tissue biomechanics.

2023

Curvature-induced cell rearrangements in biological tissues

Yuting Lou, Jean-Francois Rupprecht, Sophie Theis, Tetsuya Hiraiwa, and Timothy E. Saunders

Physical Review Letters, 2023, doi: 10.1103/PhysRevLett.130.108401

On a curved surface, epithelial cells can adapt to geometric constraints by tilting and by exchanging their neighbors from apical to basal sides, known as an apico-basal topological transition 1 (AB-T1). The relationship between cell tilt, AB-T1s, and tissue curvature still lacks a unified understanding. Here, we propose a general framework for cell packing in curved environments and explain the formation of AB-T1s from the perspective of strain anisotropy. We find that steep curvature gradients can lead to cell tilting and induce AB-T1s. Alternatively, pressure differences across the epithelial tissue can drive AB-T1s in regions of large curvature anisotropy. The two mechanisms compete to determine the impact of tissue geometry and mechanics on optimized cell rearrangements in 3D.

Link to github repository : CellPacking

Multiscale modeling of morphogenesis: force transmission and channelling during epithelial invagination

Sophie Theis

Thesis

2022

Morphogenesis includes all the events driving changes in the shape of an organism. Tissue modifications are based on cell rearrangement and cell shape changes, which are orchestrated by interactions between mechanical forces and chemical signals to allow the formation of different tissues with various functions. Vertex models play an important role in the study of morphogenetic mechanisms. They make it possible to address certain questions that are not always possible to test in vivo due to technical limitations. They can also have a predictive role on the behaviour of a tissue. I participated in the development of a modelling library called Tyssue, offering different modules in order to give the possibility to biologists to create their own model with its own dynamics. I have also worked on two morphogenetic models of fold formation in Drosophila: mesoderm invagination in the embryo and fold formation in the leg imaginal disc. I characterised the role of the different forces (apical and apico-basal) and tested their importance in the formation of mesoderm invagination. Then, I became interested in a force channelling mechanism ensuring the robustness of fold formation in the leg imaginal disc. By a combination of experimental and modelling approaches, we were able to show that the channelling of these forces is driven by the polarity of cells from the future fold, which allows preferential transmission in the direction of the fold. During the formation of the fold, forces are transmitted from one cell to its neighbours, which propagates a deformation throughout the tissue. I am interested in modelling this mechanical response of cells during force transmission. Finally, I worked on the development of a 3D apical cell surface segmentation program, in order to perform morphological analysis of the apical cell surface in 3D tissue. All of these different projects have made it possible to better understand the fundamental mechanisms governing the mechanics of tissues during their remodelling.

Keywords: epithelial morphogenesis, modelling, force, myosin II

Force-generating apoptotic cells orchestrate avian neural tube bending

Daniela Roellig, Sophie Theis, Amsha Proag, Guillaume Allio, Bertrand Bénazéraf, Jérôme Gros, Magali Suzanne

Developmental Cell, 2022, doi:10.1016/j.devcel.2022.02.020

Apoptosis plays an important role in morphogenesis, and the notion that apoptotic cells can impact their surroundings came to light recently. However, how this applies to vertebrate morphogenesis remains unknown. Here, we use the formation of the neural tube to determine how apoptosis contributes to morphogenesis in vertebrates. Neural tube closure defects have been reported when apoptosis is impaired in vertebrates, although the cellular mechanisms involved are unknown. Using avian embryos, we found that apoptotic cells generate an apico-basal force before being extruded from the neuro-epithelium. This force, which relies on a contractile actomyosin cable that extends along the apico-basal axis of the cell, drives nuclear fragmentation and influences the neighboring tissue. Together with the morphological defects observed when apoptosis is prevented, these data strongly suggest that the neuroepithelium keeps track of the mechanical impact of apoptotic cells and that the apoptotic forces, cumulatively, contribute actively to neural tube bending.

Link to github repository : AvianNeuralTubeBending

Tyssue: an epithelium simulation library

Sophie Theis, Magali Suzanne, Guillaume Gay

JOSS, 2021, doi:10.21105/joss.02973

The tyssue Python library seeks to provide a unified interface to implement bio-mechanical models of living tissues. Its main focus is on vertex based epithelium models. tyssue allows to model the mechanical behavior of 2D, apical 3D or full 3D epithelia based on the numerical resolution of the equations of motion for the mesh vertices. Biological processes are modeled through changes in the topological and dynamical properties of the mesh. tyssue is a modular library. Starting with the same tissue geometry, the choice of constraints, energy potential terms and parameters increases the possibility to answer different biological questions and easily explore mechanical hypotheses.

Link to github repository : Tyssue

Arp2/3-dependent mechanical control of morphogenetic robustness in an inherently challenging environment

Emmanuel Martin, Sophie Theis, Guillaume Gay, Bruno Monier, Christian Rouvière, Magali Suzanne

Developmental Cell, 2021, doi:10.1016/j.devcel.2021.01.005

2021

Epithelial sheets undergo highly reproducible remodeling to shape organs. This stereotyped morphogenesis depends on a well-defined sequence of events leading to the regionalized expression of developmental patterning genes that finally triggers downstream mechanical forces to drive tissue remodeling at a predefined position. However, how tissue mechanics controls morphogenetic robustness when challenged by intrinsic perturbations in close proximity has never been addressed. Using Drosophila developing leg, we show that a bias in force propagation ensures stereotyped morphogenesis despite the presence of mechanical noise in the environment. We found that knockdown of the Arp2/3 complex member Arpc5 specifically affects fold directionality while altering neither the developmental nor the force generation patterns. By combining in silico modeling, biophysical tools, and ad hoc genetic tools, our data reveal that junctional myosin II planar polarity favors long-range force channeling and ensures folding robustness, avoiding force scattering and thus isolating the fold domain from surrounding mechanical perturbations.

Link to github repository : Polarity

Mechanical impact of epithelial−mesenchymal transition on epithelial morphogenesis in Drosophila

Mélanie Gracia, Sophie Theis, Amsha Proag, Guillaume Gay, Corinne Benassayag, Magali Suzanne

Nature Communications, 2019, doi:10.1038/s41467-019-10720-0

2019

Epithelial−mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. Intriguingly, EMT is often associated with tissue invagination during development; however, the impact of EMT on tissue remodeling remain unexplored. Here, we show that at the initiation of the EMT process, cells produce an apico-basal force, orthogonal to the surface of the epithelium, that constitutes an important driving force for tissue invagination in Drosophila. When EMT is ectopically induced, cells starting their delamination generate an orthogonal force and induce ectopic folding. Similarly, during mesoderm invagination, cells undergoing EMT generate an apico-basal force through the formation of apicobasal structures of myosin II. Using both laser microdissection and in silico physical modelling, we show that mesoderm invagination does not proceed if apico-basal forces are impaired, indicating that they constitute driving forces in the folding process. Altogether, these data reveal the mechanical impact of EMT on morphogenesis.

Link to github repository : Invagination

Figure Discussion - Schéma Bilan TEM-Apoptose.png