How to fold an embryo

A new mathematical model allows researchers to simulate key processes in early animal development.
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Cells have the power to organise themselves to form complex and stable structures, whether it is to create a fully shaped baby from a single egg, or to allow adult salamanders to grow a new limb after losing a leg. This ability has been scrutinised at many different levels. For example, researchers have looked at the chemical messages exchanged by cells, or they have recorded the different shapes an embryo goes through during development. However, it is still difficult to reconcile the information from these approaches into a description that makes sense at multiple scales.

When an embryo develops, sheets of cells fold and unfold to create complex 3D shapes, like the tubes that make our lungs. Moulding sheets into tubes relies on interactions between cells that are not the same in all directions. In fact, two types of asymmetry (or polarity) guide these interactions. Apical-basal polarity runs across a sheet of cells, which means that the top surface of the sheet differs from the bottom. Planar cell polarity runs along the sheet and distinguishes one end from the other. For instance, apical-basal polarity marks the inner and outer surfaces of our skin, while planar cell polarity controls the direction in which our hair grows.

Nissen et al. set out to investigate how these polarities help cells in an embryo organise themselves to form complicated folds and tubes. To do this, simple mathematical representations of both apical-basal and planar cell polarities were designed. The representations were then combined to create computer simulations of groups of cells as these divide and interact with each other.

Simulations of ‘cells’ with only apical-basal polarity were able to generate different shapes in the ‘tissues’ produced, including many found in living organisms. External conditions, such as how cells were arranged to start with, determined the resulting shape. With both apical-basal and planar cell polarities, the simulations reproduced an important change that occurs during early development. They also replicated how the tubes that transport nutrients and oxygen form.

These results show that simple properties of individual cells, such as polarities, can produce different shapes in developing tissues and organs, without the need for a complicated overarching program. Abnormal changes in cell polarity are also associated with diseases such as cancer. The mathematical model developed by Nissen et al. could therefore be a useful tool to study these events.