JNK signaling (red) and transdetermination (green) overlap.


A dose of the JNK kinase can reset chromatin states and turn leg into wing, according to Nara Lee, Renato Paro (University of Heidelberg, Germany), and colleagues. The pathway may help cells to become reprogrammable when they find themselves in areas of injury or developmental transition.JNK has for some time been known to turn on during wound healing, and Polycomb group (PcG) proteins are known to maintain cell fates by clamping down on chromatin. But the two have never been united in one experimental design.

The Heidelberg team took a look at the two processes in fly imaginal discs—the embryonic tissues that will eventually turn into adult structures such as legs. A fraction of the leg imaginal discs are known to transdetermine—or change to a wing cell fate—when they are transplanted and wounded. In the new experiments, transdetermination rates were increased in PcG mutants but decreased in JNK mutants.

Transdetermined cells overlapped with cells high in JNK signaling and low in PcG activity. Furthermore, JNK expression down-regulated PcG proteins in both fly cells and mouse fibroblasts.

This experimental system—transdetermination during imaginal disc transplantation—is extremely artificial and not a substrate for natural selection. So where does this fit into normal fly and human biology?

Paro notes that JNK is turned on during injury and major developmental events such as dorsal and thorax closure. These are both times when cells may need to switch allegiances and take up new fates. The JNK pathway and its down-regulation of PcG proteins may open up the cell to new possibilities and allow it to fit into a new environment. Judicious manipulation of this process may, in the future, help researchers to manipulate the differentiation of various adult stem cells.


Lee, N., et al. 2005. Nature. doi:.