By Rachel Ehrenberg
Building a face is no small task — the cells that will become its bone, cartilage, muscle and nerves must travel far from their origin in the developing embryo before colonizing the head.
While much research has focused on the fate of these cells, developmental biologist Dominique Alfandari is more interested in their journey. The scientist from the Department of Veterinary and Animal Sciences has received $1.7 million from the National Institutes of Health (NIH) to investigate the molecules that may be regulating their cellular migration to the head. The research should contribute to our understanding of what leads to abnormalities in head and face development, and shed light on invasive migrations, such as those of cancer cells.
The steps from a seemingly formless egg to a large and complex organism are many—cells divide, re-arrange themselves, divide some more, there are chemical signals to receive and send—depending, for example, on whether it’s time to develop a nervous system or time to develop skin. Proteins are key players in the various events that lead to a fully formed organism and a particular family of proteins already implicated in a number of developmental processes also appears to play a role in the cellular migration of the future face cells, called cranial neural crest (CNC) cells.
Some of these proteins—dubbed ADAM proteins—appear to be guiding the CNC cells on their migration to the head, says Alfandari. “We know that if we block one of these proteins—ADAM13—we no longer get normal cell movement.”
ADAM13 has been detected on the surface of CNC cells while they are migrating. And the protein can sever other proteins and can promote adhesion, capabilities that come in handy when directing cell movement. But the specifics of ADAM13’s actions are still unclear. Alfandari will explore ADAM13’s regulatory capabilities with the NIH funding.
“Our working hypothesis is that ADAM13 cuts another protein that prevents CNC cell migration until the time is right,” says Alfandari. “This protein might hold the CNC cells like an anchor, or block their path in some way.”
The research is intriguing to Alfandari for many reasons; improper CNC migration can lead to a multitude of developmental problems related to bone formation in the face. And ADAM proteins keep showing up where cells are migrating, a recent study found them helping cancer cells invade a liver. “Right now there’s not much to be done when cancer invades organs, says Alfandari. “If we can figure out how to inhibit these proteins, perhaps we could prevent such invasions.”