Researchers have uncovered a new mechanism by which the physical shape of cells influences how they communicate during development, revealing that three-dimensional cell geometry can directly regulate a major signalling pathway that controls tissue patterning.
Published in Proceedings of the National Academy of Sciences (PNAS), the study demonstrates that epithelial cells in the developing fruit fly wing use their complex 3D architecture to expand the range of contact-based signalling through the Notch-Delta pathway, a fundamental communication system conserved across animals. The work provides new insight into how tissue mechanics and cell geometry interact to shape biological pattern formation.
“Cell communication is often studied in terms of molecular signals alone,” said Dr Giulia Paci. “Our findings show that the physical structure of cells—their shape and the geometry of their contacts—can fundamentally change how signalling occurs inside tissues.”
Cells in multicellular organisms rely on communication with neighbouring cells to coordinate growth, differentiation, and tissue organization. One of the most important pathways governing these processes is Notch-Delta signalling, which typically operates through direct contact between adjacent cells.
Using the developing wing margin of Drosophila melanogaster (fruit fly) as a model system, the researchers discovered that epithelial cells contact different neighbouring cells at different heights along their apical-basal axis. This layered organisation effectively increases the number of neighbouring cells that each cell can communicate with.
To analyse how these interactions influence developmental patterning, the team developed a computational framework called the Multilayer Signalling Model, which simulates signalling across experimentally derived 3D cellular topologies. The model predicted that signalling along the lateral surfaces of cells plays a crucial role in controlling the spacing of sensory organ precursors (SOPs), specialized cells that later develop into sensory structures. Experimental tests confirmed the prediction: altering cortical stiffness and cell surface tortuosity in living tissues changed SOP spacing in vivo.
The findings identify a previously unrecognized feedback mechanism linking tissue mechanics and cell communication. By changing the stiffness of the lateral cell cortex, cells alter their geometry and contact patterns, which in turn modifies their ability to participate in signalling interactions.
Because cell shape and tissue architecture are influenced by developmental history and mechanical forces, the researchers say the implications extend well beyond the Notch-Delta pathway. “This work highlights how the physical organization of tissues can actively regulate signalling outcomes,” said Prof Yanlan Mao “The principles we uncovered may apply broadly to developmental systems and diseases where tissue mechanics and cell communication are disrupted.”
The study also demonstrates the importance of incorporating realistic three-dimensional tissue architecture into models of developmental signalling, rather than relying solely on simplified two-dimensional representations.