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Silenced gene in worm shows role in regeneration

SALT LAKE CITY -- Researchers at the University of Utah have discovered that when a gene called smedwi-2 is silenced in the adult stem cells of planarians, the quarter-inch long worm is unable to carry out a biological process that has mystified scientists for centuries: regeneration.

The study published in the Nov. 25 issue of Science was led by Alejandro Snchez Alvarado, Ph.D., Howard Hughes Medical Institute investigator and professor of neurobiology and anatomy at the U of U School of Medicine, and carried out by members of his laboratory, in particular Helen Hay Whitney Foundation post-doctoral fellow Peter W. Reddien who is now an Associate Member at the Whitehead Institute for Biomedical Research.

Elimination of smedwi-2 not only leads to an inability to mount a regenerative response after amputation, but also to the eventual demise of unamputated animals along a reproducible series of events, that is, regression of the head tip, curling of the body and tissue disintegration. These defects are very similar to what is observed after the planarian stem cells are destroyed by lethal doses of irradiation. The key difference, however, is that the irradiation-like defects observed in animals devoid of smedwi-2 occur even though the stem cells are still present in the organism.

This finding suggests something surprising: the instructions that a daughter stem cell needs to differentiate for regeneration or for maintaining tissue structure begin to be defined at the time of division of its parent cell. "Once the smedwi-2 molecule is eliminated, the animal is destined to die since the functions of the daughter cells are severely compromised" said Snchez Alvarado.

The study follows a landmark work that he and Reddien published last spring in Developmental Cell, in which, using a method of gene silencing called RNA interference (RNAi), the researchers silenced more than 1,000 planarian genes, some of which they identified as essential
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Contact: Alejandro Sanchez Alvarado
sanchez@neuro.utah.edu
801-913-8430
University of Utah Health Sciences Center
24-Nov-2005


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