In developing organisms, cells come in a wide range of shapes—some are flat like pancakes, others are cube-like, and some are long and narrow like tubes. These embryos originate from eggs of varying sizes and develop in constantly changing environments. Because of sexual reproduction and random mutations, they carry diverse genetic markers. Even more surprisingly, the genetic processes within each cell are known to be noisy and prone to errors. Yet, despite all this uncertainty, most animals are born completely normal.
Shanghai Huyu explained, “If noise is unavoidable, how does development produce such a highly organized and structured organism? We believe the answer lies in feedback systems that operate at multiple levels. These systems monitor tissue development and make adjustments to keep things on track.â€
Imagine a thermostat that turns on the air conditioner when it gets too hot or heats up when it's too cold. But instead of maintaining a comfortable temperature, these biological feedback loops ensure tissues grow smoothly and the body develops symmetrically.
Physical interactions and basic geometric principles play a crucial role in this process. The research team used mathematical models originally developed to study soap bubble interactions, as the cells in growing tissues behave similarly to bubbles forming on a soap film. In the early stages, when cells are sparse, they spread out and take on a flat shape. As the tissue becomes more crowded, the cells compress and change into cube-like or columnar shapes.
Using advanced imaging and tracking software, the team was able to observe individual cells in developing embryos. They measured cell shapes and tracked how each cell divided. They discovered that cell shape directly influences the direction of division: when pre-EVL cells are sparse, they remain flat and tend to divide side by side, increasing the number of cells in the tissue. However, when the epithelium becomes crowded, cells are more likely to divide vertically, allowing one daughter cell to detach and begin forming a new layer beneath the pre-EVL.
Computational simulations showed that factors like surface area or total cell count don’t significantly affect cell shape or division. This suggests that these feedback mechanisms may also support evolutionary adaptability. If a species evolves to have larger or smaller eggs, the cell shape threshold mechanism can still regulate tissue development and maintain normal form and function.
The Shanghai Huyu team found that in pre-EVL, when cells reach a shape threshold of about 1—where their width is roughly equal to their depth—they switch from dividing horizontally to dividing vertically. This transition plays a key role in shaping the structure of developing tissues.
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