It has long been thought that cells that regenerate tissue do so by regressing to a developmentally younger state. Now two University of Washington researchers have demonstrated that cells can regenerate without becoming “younger.” Biologists for years have studied stem cells, the ones responsible for replenishing and regenerating an organism’s structures, aiming to find the means to selectively regenerate tissue such as that of the heart or liver in much the same way that the body heals a broken leg. Much hope rests with non-embryonic stem cells, which can renew themselves and, within limits, produce all the specialized cell types from the type of tissue in which they originate. But scientists have puzzled over just how such cells function, how they can be spurred to create new tissue, and just when in their development it is determined what tissue they can produce. Gerold Schubiger, a UW biology professor, and Anne Sustar, a research technician in his laboratory, used groups of cells, called imaginal discs, in fruit fly larvae to provide an easily controlled system to study regeneration. Imaginal discs convert genetic information that determines the specific tissue into which the cells will develop in the adult fly. For example, leg discs form only adult legs and wing discs form only adult wings. Normally, all of those cells develop into that specific tissue, either when the fly reaches the adult stage or when regenerating a lost structure, such as parts of a leg disc. The exception is a very small number of cells in each disc, located at what the researchers term the “weak point.” These cells change their ultimate destiny, or fate, as the disc regenerates tissue so that, for example, instead of regenerating leg structures they form wing structures. Such fate changes are known as transdetermination, and they demonstrate that a few cells have development potential that is adaptable rather than firmly fixed, Schubiger said. That has parallels in the adaptable development potential found in some vertebrate stem cells, he said. In the case of the fruit flies, regeneration and transdetermination begin in the “weak point” of the leg imaginal disc when a signaling gene called wingless activates a selector gene called vestigial, which spurs wing development in that stem cell-like region.
