About face: Study shows long-ignored segments of DNA play role in coordinating early stages of face development

The human face is a fantastically intricate thing. The billions of people on the planet have faces that are individually recognizable because each has subtle differences in its folds and curves. How is the face put together during development so that, out of billions of people, no two faces are exactly the same?

School of Medicine researcher Joanna Wysocka, PhD, and her colleagues have discovered key genetic elements that guide the earliest stages of the process.

Their research, published in the Sept. 13 issue of Cell Stem Cell, provides a resource for others studying facial development and could give insights to the cause of some facial birth defects. Because there is not enough genetic information in the body to define exactly where each cell will go, development of the face proceeds much like origami: genes provide instructions for folding, crimping, and movement of cells. As with origami, following a sequence of simple instructions can result in a complex, intricate object.

Wysocka focused on the first critical fold in the process of making an embryo, when the whole of the embryo is a flat sheet of cells that creases and closes over on itself to make a tube. Much of the tube eventually becomes the foundation of the brain and the spinal column, but one end sets the stage for the formation of the head and face. This process is driven by a small population of remarkable cells called neural crest cells.

"We were interested in identifying the portions of the human genome that are responsible for the behavior of the neural crest," Wysocka said.

What they discovered is that the modification of a collection of DNA sequences called “enhancers” can dial up or down the activity of the genes governing which cells eventually become the face. It’s almost as if they have discovered how the instructions for a piece of origami can be modified — slightly change how a fold is made and you may end up with something very different looking.

Researchers have identified five of the genes that shape a person’s face, work that could help scientists better understand facial abnormalities like cleft palate and someday might even help forensic investigators determine what a criminal suspect looks like from crime-scene DNA.

Researchers previously knew that genetics played a large role in determining face shape, since identical twins share DNA. However, little was known about exactly which genes are involved. Three genes were thought to have roles in the arrangement of facial features, and the new research confirmed their involvement. It also identified two other genes.

"We are marking the beginning of understanding the genetic basis of the human face," said lead researcher Manfred Kayser, head of the forensic molecular biology department at Erasmus MC-University Medical Center Rotterdam, Netherlands.

The study is part of the work of the International Visible Trait Genetics (VisiGen) Consortium, a group of six researchers who want to understand the genetics behind visible human characteristics.