Cells acquire different shapes and adhere to each other in different ways depending on their function and on their microenvironment in a living organism. Cells’ ability to assemble together with various geometries gives rise to diverse tissue shapes, such as the thin wings of the dragonfly, the branched network of the human lung or the faceted eye of the fly. Exactly one century ago, in his seminal book “on Growth and Form”, D’Arcy Thomson hypothesised that general physical and mathematical principles might explain the diversity of tissue and organism shapes. One of the main principles is that surface tension between cells is critical to explain shape. We know today that the mechanical tension at the contact between cells relies on two biological systems: contractile cytoskeletal networks, which generate force, and adhesion bonds, which support the contact between cells. How these two systems regulate cell shape is still a matter of debate. How do cells expressing different types of adhesion molecules organize their contacts in a compact tissue? To which extent do adhesion bonds contribute to tension in vivo?
To address these questions, we have used the compound eye of the fruit fly, which presents a quasi-hexagonal array of about 800 facets, each of which comprising different types of cells.
In this model system, we have measured the concentration of adhesion molecules and of the molecular motor Myosin-II. Using laser nanodissection, we have determined the tensions at different cell-cell contacts, between cells of the same type (homotypic contacts) and between cells of different types (heterotypic contacts). Integrating these data in a mechanical model, we have predicted cell shapes and cell arrangements in the wild type, as well as mutant conditions for which adhesion or contractility was perturbed.
We show that Myosin-II contractile forces have a 2- to 5-fold larger contribution to tension than adhesion molecules. However, N-cadherin has an indirect control on cell shape by regulating Myosin-II contractility. At homotypic contacts, N-cadherin bonds downregulate Myosin-II contractility. At heterotypic contacts with E-cadherin, unbound N-cadherin induces an asymmetric accumulation of Myosin-II, which leads to a highly contractile cell interface. Such differential regulation of contractility is essential for morphogenesis as loss of N-cadherin disrupts cell rearrangements. Our results establish a quantitative link between adhesion and contractility during morphogenesis in vivo.
The next step is to understand how differences in cell surface molecules (here adhesion molecules) control Myosin-II, and thus cell-cell contacts and cell shapes. Our work has implications in many contexts including lineage sorting, elimination of misspecified cells and epithelial-mesenchyme transition.
To know more
Patterned cortical tension mediated by N-cadherin controls cell geometric order in the Drosophila eye
Eunice H.Y. Chan, Pruthvi C. Shivakumar, Raphaël Clément, Edith Laugier and Pierre-François Lenne
Institut de Biologie du Développement de Marseille
CNRS UMR 7288 – Aix Marseille Université
Campus de Luminy. Case 907
13288 Marseille cedex 9
04 91 26 93 65