Homeobox Gene Siamois Linked To Master-Control Cells In Early Embryo

December 09, 1997

On a molecular level, what happens in vertebrate development between fertilization and the formation of a mass of cells called the organizer that controls the identity and arrangement of embryonic cell types is still somewhat of a mystery. A recent study by Daniel S. Kessler, PhD, assistant professor of cell and developmental biology, has been able to fill in some of the missing biochemical pieces. He found that activation of siamois -- a member of the homeobox family of genes important in guiding development -- is required for the formation of Spemann's organizer, the cluster of these master-control cells in frogs. (The first Nobel Prize in physiology or medicine for the field of developmental biology -- awarded in the 1935 -- was for the discovery of Spemann's organizer.)

Siamois is turned on by a series of proteins made by genes involved in the wnt signal transduction pathway, also important in development. Wnt genes have also been implicated in certain breast cancers. "What the wnt genes do is turn on the production of siamois in a localized region of the embryo," explains Kessler. "The transcription factor encoded by the siamois gene goes on to activate a whole group of organizer genes. In the absence of this factor, the organizer doesn't form. The embryo fails to form muscle and neural tissue and develops with no head-to-toe or front-to-back organization."

Kessler is now looking for siamois gene homologues in mice and other vertebrates. He also plans experiments using knockout mice once the mouse homologues are identified. This work appeared in the November 25 issue of the Proceedings of the National Academy of Sciences.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation. In federal fiscal year 1996, the medical center received $149 million. In addition, for the second consecutive year, the institution posted the highest growth rate in research activity -- 9.1 percent -- of the top-ten U.S. academic medical centers during the same period. News releases from the medical center are available to reporters by direct E-mail, fax, or U.S. mail, upon request. They are also posted to the center's webpage (http://www.med.upenn.edu) and EurekAlert! (http://www.eurekalert.org), a resource sponsored by the American Association for the Advancement of Science.

University of Pennsylvania School of Medicine

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