Harvard Researchers Discover New Genetic Source of Tissue Formation

Harvard researchers wrote in a study published Friday that morphogenesis – the embryonic process through which cells are distributed into different tissues and organs – is controlled by “adhesion molecules” that direct specific cells to stay connected.

The finding could have momentous implications for developing disease treatments, according to experts, allowing for a better understanding of how cells divide and form larger tissues.

The study — conducted by members of Systems Biology professor Sean Megason’s lab — examined three types of zebrafish cells that have the capacity to split into different types of neural system cells. Megason likened the process of morphogenesis carried out by these cells to the building of Legos on a “blank canvas.”

The team found that cells of similar types were more attracted to each other and discovered the existence of “adhesion codes” — combinations of genes that dictate cell types’ attractive forces towards one another.

The team directly tested the adhesion forces between certain cell types by placing them next to each other and measuring the approximate force necessary to pull them apart. Megason said the experiment was similar to the separation of oil and water molecules.

“That idea is kind of like salad dressing with oil and water,” Megason said. “So if you shake up oil and water, it’ll separate.”

“The idea was that cells might have different stickiness,” he added. “And then based on what they like to stick to, it'll sort into different groups.”

Sahand Hormoz, a Harvard Medical School systems biology professor unaffiliated with the study, wrote in an email the findings will heavily impact work on tissue and organ creation.

“This work has far reaching implications for tissue engineering and synthetic biology,” Hormoz wrote. “For a multitude of translational applications, we would like to be able to generate organs and tissue in a dish. It is almost impossible to engineer these complex structures without understanding the mechanisms that they use to organize.”

Carl-Philipp Heisenberg, a professor at the Institute of Science and Technology Austria and co-author of the study, said the team considered the French flag model, which assumes that certain specialized molecules direct cells to behave in specific ways during morphogenesis. But the new study concluded that in fact, adhesion codes are responsible for the cells’ patterns of separation.

Megason said the research could have significant clinical impact, from increasing understanding of how cancer cells form shapes to building tissues for organ transplant and tissue replacement.

“Once we understand the basic role that cells used to organize themselves to form structures, it can have a wide range of clinical applications,” Megason said.

—Staff writer Ethan Lee can be reached at ethan.lee@thecrimson.com.