Roundworm studies yield new insight into organ formation

June 10, 1999 -- While studying the modest roundworm C. elegans, researchers have pinpointed an enzyme that controls the shape of a developing organ. This discovery opens the way for researchers to gain new understanding of the mechanisms by which organs blossom from single cells.

HHMI investigator Judith Kimble and colleague Robert Blelloch, both of the University of Wisconsin-Madison, report in the June 10, 1999, issue of the journal Nature, that a metal-containing enzyme called a metalloprotease guides the formation of gonads in the roundworm C. elegans. The enzyme is crucial for ensuring the proper elongation and curvature of the gonads.

The researchers began their experiments by isolating a gene that codes for GON-1, a protein that is required for normal gonad formation. Analysis of the protein revealed that it is a metalloprotease -- a type of metal-containing enzyme that snips apart other proteins. After tinkering with the enzyme to jam its operation, Kimble and Blelloch concluded that the protein-snipping activity is needed by the enzyme to perform its critical organ-forming functions.

To illuminate what else this protein was doing in the developing worm, the scientists constructed a fluorescently-labeled version of the enzyme that lights up when viewed under ultraviolet light. Then, using the modified enzyme, they traced the protein's expression within the developing worm.

"We found that the metalloprotease was expressed in leader cells (located at the tip of the gonad), which made a lot of sense because they are part of the developing gonad," said Kimble. "But we also found that it was expressed in the body wall muscle, which didn't make a lot of sense to us. So, we then asked what was important about these two distinct activities, since quite frankly, we were not expecting the body wall muscle expression to be important in gonad

Contact: Jim Keeley
Howard Hughes Medical Institute

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