U.Va. Researchers Working to Understand Embryonic Development

May 14, 2007 -- In science, proximity can produce serendipity. That has certainly been the experience of Judith White and Douglas DeSimone, professors in the Department of Cell Biology. Because of their proximity, they were able to perceive that areas of their research had overlapped, encouraging them to collaborate on a project that ultimately may produce a new tool to fight birth defects. “This collaboration is the real deal,” DeSimone comments. “It’s tremendously rewarding and productive.”

White has long been interested in a process called cell membrane fusion, by which two membrane-bounded compartments, for example two cells, become one. She studies the way viruses fuse with cells to inject their infectious nucleic acid into them, and she has been interested in the type of cell-to-cell fusion typified by fertilization. DeSimone, in his laboratory next door, studies morphogenesis, the mechanisms that organize cells into functional, three-dimensional tissues and organs. He is particularly interested in the migration of cells in animal embryos during early stages of development. This process involves a class of proteins called integrins that bind cells to a particular spot on the supporting framework of extracellular proteins that helps give these tissues their shape.

Fifteen years ago, White identified a class of proteins called ADAMs (because they have a disintegrin and a metalloprotease domain and in honor of their origin in the field of fertility). There are 22 members of the ADAM family in human beings. Some serve as biochemical scissors, cutting proteins emerging from the cell membrane into active molecules that circulate among other cells promoting growth, inflammation, and other biological processes. Others help regulate the way cells adhere and signal to each other.

“Essentially, ADAMs play an important role in the way cells communicate,” White says. This makes them an important target for drug discovery. Control ADAMs, and you can control that communication, enabling you to cut off signaling pathways that, when poorly regulated, can cause cancer or autoimmune diseases like rheumatoid arthritis.

DeSimone’s work suggests another important role for ADAMs. DeSimone studies the migration of cranial neural crest (CNC) cells through the developing head, a process that ultimately gives rise to the bone, cartilage, nerves, and connective tissue of the face. Several years ago, White and DeSimone began looking for ADAMs that might be involved in embryo development. This work resulted in the discovery of a novel member of the ADAM family, ADAM 13, that is highly expressed in CNC cells, where it functions in their migration.

 Together they are investigating the different ways that ADAM 13 regulates the molecular signaling responsible for CNC cell migration — and they are motivated by more than curiosity. If they can understand the role that ADAM 13 plays, they may be able to prevent birth defects like cleft palate. “This is an exciting challenge,” says White. “You never know where basic research will lead you — even if it’s to the laboratory next door.”

Written by Charlie Feigenoff, a freelance writer in Charlottesville.