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Jefferson researchers uncover biochemical clues to how cells migrate in embryos

sterol synthesis in both humans and zebrafish.

Using a special technique developed by a colleague, they actually visualized the effect of Lipitor on germ cells, which, he says, caused the cells to "get lost." The cells were unable to migrate to the correct place in the developing embryo. Dr. Farber's group found that HMG-CoAReductase is important not just for fly germ cell migration, but also for a model vertebrate system such as the zebrafish. These data, he says, suggest that this pathway is "a highly conserved feature" of animal development.

The researchers found that they could block the effects of Lipitor if they injected the zebrafish beforehand with mevalonate, which is what HMGCoAReductase makes. They continued along the pathway, step by step, chemically knocking out enzymes and replacing them with their products to see if they could restore the normal pathway. They subsequently determined that blocking a particular enzyme, geranylgeranyl transferase I, which is further along the pathway from HMG-CoAReductase and responsible for transferring a lipid to a target protein a process called prenylation resulted in abnormal germ cell migration.

The work may have larger implications. "It's still preliminary, but we suspect that this pathway is a model for long-range migration of cells in general," he says. "We've identified a pathway, but not the particular protein that is modified. This is a protein that needs a lipid added in order to enable migrating cells to find their home." He and his team currently are trying to identify this mystery protein.

It is also possible that this pathway is important in cancer metastasis. "It's a commonly held view among scientists that many pathways common to cancer are in some regard a recapitulation of the pathways involved in early development," says Dr. Farber. "A cancer cell growing out of control needs to metastasize to other areas to set up shop. We suspect this pathway is what enables a cance
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
16-Feb-2004


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