BUSM Researchers understand the basic biology of how cells are guided to move in particular way

In a paper titled, “PDGF-A Interactions With Fibronectin Reveal A Critical Role For Heparan Sulfate In Directed Cell Migration During Xenopus Gastrulation” (PNAS early edition December 4), a collaboration between the research groups of Dr. Karen Symes, an associate professor of biochemistry, and Dr. Matthew A. Nugent, a professor of biochemistry, examined how the interaction of specific molecules form a path that can guide cells to travel in a particular direction. This information is important because such directed cell movement plays pivotal roles in normal processes such as embryonic development and also in abnormal events such as cancer metastasis. Similar molecules are thought to control both normal and abnormal processes.

In the study, Erin Smith, a biochemistry graduate student, used cells that normally form the facial muscles of the developing embryo. These cells need to travel to the proper place at the correct time to fulfill their role. It was previously known that these cells move across a layer of different cells that are coated with a molecule called fibronectin. In addition, another molecule called platelet-derived growth factor (PDGF) was known to guide the cells. “We have now found that in order for PDGF to be able to guide these cells, a further molecule called heparan sulfate is required,” said Symes. “Our experiments suggest that heparan sulfate makes an alteration in the structure of the fibronectin that reveals sites where PDGF can bind to it, creating a path that cells can follow in order to find their way,” she added.

According to Symes, an innovative aspect of this work was that cells were examined in a tissue environment, which is essential to learning how cells, which rarely act in isolation, behave in the body.