How do organs such as the lungs or kidneys generate the intricate, treelike internal anatomy essential to their function? To find out, Celeste Nelson developed a lab technique for growing structures from simple shapes like the ones from which organs begin developing in the embryo. Nelson knew, for example, that lungs begin as an inverted Y. By experimenting with different shapes, such as a T instead of a Y, she discovered that the exact form of these initial structures plays a pivotal role in how the tissue’s sophisticated architecture develops. Different starting shapes produce different patterns and concentrations of signaling molecules. The molecules cause growing branches to repel each other. Subsequent mechanical stresses in the branches determine where new branches will begin to develop and, in turn, produce their own signaling molecules. Other researchers had previously theorized that geometry matters in tissue development. But Nelson’s technique–adapted from a process originally used to make computer chips–allowed her to prove it for the first time, and to spell out the mechanism involved.
Nelson, now an assistant professor of chemical engineering at Princeton, has worked with her group to identify several genes that need to be present and functional for branching tissue to develop properly, and they are trying to figure out how those genes work together to orchestrate the process. She hopes that understanding how branching normally happens will reveal ways to intervene when it goes awry. Recent work has shown, for example, that the signals that spur branching–which are typically silent once development is complete–are reawakened in some tumors. In addition, her techniques for building three-dimensional tissue structures could ultimately be used to help engineer replacement organs. –Jocelyn Rice
Form and function: Organs grow from small cell clusters. By using different stamps (top left) to vary the shapes of these clusters, Celeste Nelson is teasing out how important tissue structures develop. Bottom left: starting shapes; right: growing and branching tissue network.
Credit: Emily Cooper