Tufts Scientists Reveal How Molecules Shape Cells, Cells Move to Shape Tissue

New research delves into the role of PIP3, a vital molecule, in driving cellular shape and tissue organization.
A slide imagine showing PI3K and PIP3
Top images show an accumulation of PI3-Kinase—the enzyme that generates PIP3—and PIP3 accumulating along the edges of adjacent cells as their contact expands. Bottom images show a decrease in PI3-kinase and PIP3 as the contact contracts.

A team of biomedical researchers at Tufts University School of Medicine (TUSM) have made a groundbreaking discovery about how certain molecules move within cells to shape them and ultimately form animal tissues. Their research, published in Developmental Cell, uncovered the mechanisms that drive cellular shape and tissue organization.

The paper focuses on a molecule called PIP3, a type of phospholipid generated at the cell membrane that acts as signal transducer, which helps cells interpret signals and organize a response to regulate cell shape changes. “By using live imaging, to track these molecules and analyze their movement over time, we have unraveled the intricate network of molecular interactions that regulate cell shape change,” describes Victor Hatini, associate professor of developmental, molecular & chemical biology and lead author of the study.

Jacob Malin, the first author of the study and primary research technician in the Hatini Lab, is not just excited about the discovery, he’s thrilled by the fact that he can see these cellular changes with his own eyes. “It’s fascinating to be able to watch, almost in real time, how different molecules move to specific sites in the cells to affect cell shape, and how these changes in cell shape influence the localization and activity of the molecules, creating a feedback loop that drives further shape changes in repeated waves.”

"Our findings challenge conventional wisdom about the role of PIP3 and its regulators in tissue development,” says Hatini. “We’ve connected PIP3 production and turnover to the regulation of the cytoskeleton–the structure that gives cells their shape–and the changes in cell behavior needed for cells to develop their final form and arrangement in tissues. This deeper understanding of PIP3 function in these fundamental processes in animal development could lead to significant advances in medical science."

Application of this new knowledge is groundbreaking for scientists working to tackle the causes of and treatments for diseases like cancer. For tissues to develop correctly, their cells must go through various stages of development to find their role within a larger tissue and align themselves properly with their neighbors. Whenever cells fail to reach their final form or “forget” their role within a tissue, it can lead to cancer. By identifying the molecules and processes that influence the development of a tissue, scientist can pave the way for innovative clinical treatments and usher in a new era of biological understanding.