UW scientists find a gene that controls organ shape

Growing complete organs in the laboratory, a longstanding dream of biomedical science, is one key step closer to reality as a team of Wisconsin scientists report the discovery of a genetic mechanism that gives organs their shape.

Writing in the Thursday, June 10, edition of the scientific journal Nature, a team of scientists from the Howard Hughes Medical Institute (HHMI) at UW–Madison describe a protein that regulates organ shape in the nematode Caenorhabditis elegans.

An organ-shaping gene has been found in the microscopic worm Caenorhabditis elegans, or C. elegans for short. The gene and the protein it makes are responsible for shaping the gonad, a complex reproductive organ. Similar genes and proteins are probably at work in other animals, including humans. The new finding by University of Wisconsin–Madison biochemist Judith Kimble and graduate student Robert Blelloch advances the prospect of one day growing complete organs for transplant.

The finding is important for two reasons, said Judith E. Kimble, an HHMI investigator, UW–Madison professor of biochemistry and co-author of the Nature report. “One reason is that very little is known about how organs are shaped and this is one of the first molecules that can be manipulated to change organ shape at will,” she said. “The second is that one of the mammalian counterparts of this organ-controlling protein may be involved in the spread of cancer cells.”

The grail of growing human organs for transplant in a laboratory dish is still a distant prospect. But with the new discovery of an organ-shaping protein, and the gene that makes the protein, a key step in the process of how nature organizes an ambiguous mass of cells into a complex organ has been identified.

Working in the microscopic worm C. elegans, a workhorse of modern biology, Kimble and Robert H. Blelloch, a doctoral and medical student in Kimble’s lab, found that a protein, dubbed GON-1, is responsible for shaping the gonad, an intricate reproductive organ.

In early development, gonads form from a grouping of four specialized cells that grow into an organ. They accomplish the task with the help of a specialized “leader cell” whose job is to set up the polarity and shape of the organ, Kimble said.

The leader cell is located at the tip of an arm of accumulating cells that migrate into the U-shaped gonad organ. In the Wisconsin study, the making of the GON-1 protein was found to be a key function of the leader cells that directed the growth of the organ.

Although the new research was conducted in one organ in a microscopic worm, Kimble said there is a good possibility that the same organ-orchestrating mechanism is common to other organs in most other animals. And with the advent of human stem cell technology in the past year, the chance that scientists might one day be able to coax cells in a dish to grow into entire organs is now enhanced.

Moreover, the discovery of the organ-shaping protein, Kimble added, yields an important clue to how cancer may spread because similar proteins may be involved in shepherding cancerous cells from a tumor to other parts of the body. When cancer spreads or metastasizes in the body, prospects for recovery are grim.

Kimble said knowing how the protein works may enable the development of inhibitors that could slow or stop the spread of cancerous cells in cancer patients.