Cells do not relive youth

Afew cells in the imaginal disc of the fly larva have the exceptional ability to transdeterminate (TD)—that is, to change fate—upon injury and regeneration. For example, injured leg precursors may form a wing instead. TD cells have many stem cell–like qualities. As stem cell multipotency is thought to be characteristic of “young” cells, it has been suggested that TD is preceded by cellular rejuvenation. Now, research from Anne Sustar and Gerold Schubiger (University of Washington, Seattle, WA) shows that no such fountain of youth is necessary. Instead, cells first adopt an unusual cell cycle profile before TD.Using injuries or ectopic expression of Wg (a Wnt mitogen that induces TD) and a wing-specific reporter, the authors isolated transdetermining cells from imaginal discs. Young cells normally cycle more rapidly than do older cells, but TD cells kept the same relatively slow doubling time that they had before the injury or Wnt induction. In this sense, at least, they were not rejuvenated.

Though division timing was unaffected, TD cells did transiently alter their cell cycle phasing; they passed quickly through G₁ and lagged in S phase. This phase change preceded TD. A longer S phase might allow time for chromatin changes that are needed for the different cell fate, and the authors propose that Wg induces chromatin remodeling proteins such as Polycomb.

Cells with the unusually long S phase were also larger than non-TD cells. Bursts of biosynthetic activity may be the driving force for the phase changes and subsequent developmental plasticity, but this remains to be shown. Forcing growth and division by overexpressing insulin pathways induced some fate changes but did not induce TD to wing. Wg may also have morphogenic properties. “We can speculate,” says Schubiger, “that Wg targets TD cells and acts as a mitogen. But we believe that only sustained Wg signaling causes a change [in cell fate].

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