How Embryonic Stem Cells Coalesce to Form the Face

Cells in the developing embryo can sense the stiffness of other cells around them, which is key to them moving together to form the face and skull, according to a study published today in Nature. Facial malformations and death can arise in embryos where the cells are unable to distinguish soft regions from hard ones, and researchers say the discovery could help to understand and prevent harmful birth defects.

 “The features of human and animal faces, like the nose, lips and ears, are sculpted by the complex and precise movement of cells in a developing embryo,” explains lead author Roberto Mayor who is from University College London.

The study was conducted using frog embryos, as their neural crest cells behave in a similar way to those of humans and their movement is often used to study the spread of cancer. In addition, the embryo development of frogs can be studied without inflicting harm.

Professor Mayor and colleagues had previously found that the stiffening of embryonic cells precipitates the migration of neural crest cells to the front of the head to form the face. Here, they have identified how the cells can detect stiffness in their surrounding environment in order to move along a stiffness gradient.

The research team identified a network of chemical and mechanical signals that interact to cooperatively control cell migration in the embryo. They found that neural crest cells induced the stiffness gradient by relying on a protein known to be involved in cell-to-cell adhesion, and they sensed the gradient by interacting with the extracellular matrix). In doing so, the cells are able to make their own path toward stiffer regions of the embryo.

“This newly identified behaviour is likely to be found not only in the cells that form our face, but in the cells that forms all our organs, and could play a central role in the dissemination of cancer cells during metastasis which hijack the behaviour,” adds co-author Adam Shellard. “Understanding how these cells move is an important step toward developing therapies for craniofacial malformations and cancer progression.”