Queing Up

Lipid is Key to Embryonic Development

A littleknown lipid plays a big role in turning a hollow sphere of stem cells into a human being, researchers have found.

They found that in the first few days of life, ceramide helps stem cells line up to form the primitive ectoderm from which embryonic tissues develop, said Dr. Erhard Bieberich, an MCG biochemist.

Probably 90 percent of ceramide gathers at the top, or apical, end of these early stem cells, giving cells direction. “We have cell polarity, an up and down, and that is what ceramide most likely regulates,” said Dr. Bieberich. “Cell polarity is absolutely essential for differentiation; otherwise, you have a ball of cells, not organized tissue.”

In fact, embryos begin as a wad of cells, but within 24 hours, some cells die and others become part of the hollow sphere with an inner layer—the primitive ectoderm—that will further differentiate into an embryo, and an outer layer—the primitive endoderm—that sustains a fetus.

“Ceramide distributes to the apical end of the cell,” said Kannan Krishnamurthy, an MCG graduate student and first author of the study published in the Feb. 2, 2007 issue of the Journal of Biological Chemistry. “In this case, the basal, or lower, end is attached to the outer layer while the apical end points toward the sphere’s cavity.”

Cells make ceramide, which researchers are finding has many jobs in the developing and mature body. Like other lipids, it helps make up membranes throughout the body, it has an insulation role in the skin and it is a precursor for the protective coating of nerves, called myelin.

“There is more and more evidence that ceramide not only is a structural lipid but a messenger involved in signal transduction, in telling proteins what to do,” said Dr. Guanghu Wang, an MCG research assistant scientist who shares first authorship.

In 2003, Dr. Bieberich and his colleagues reported ceramide teams up with the protein, PAR4, to eliminate useless cells in developing brains. Now, his team reports that ceramide is vital in establishing cell polarity by attracting certain proteins to the top of the cells, then triggering a series of interactions between them.

When researchers inhibited ceramide production, polarity proteins didn’t gather at the top of cells, cells died and primitive ectoderm formation was impaired. All processes worked like a charm when ceramide was restored. They plan to study ceramide’s potential roles in mature cells and in some cells losing their direction and becoming cancerous.

“There are conditions where a lot of cells die by what we call apoptosis and, in these cases, ceramide may be elevated, causing good cells to die,” said Dr. Bieberich. Ultraviolet radiation, for instance, may increase ceramide levels.

To study the quantity and location of ceramide, the researchers first developed an antibody that binds to it so it could be seen and counted. Previously, chemical studies have documented its presence but nothing more.

Longstanding collaborator Dr. Brian G. Condie, a developmental neurobiologist at the University of Georgia, and Dr. Jeane Silva, an MCG research coordinator, also are study coauthors. The work was funded by the National Institutes of Health.

Toni Baker

 

 

The Medical College of Georgia is the state’s health sciences university with a tripartite mission of education, research and patient care.