Although much of dedifferentiation (left) is the reverse of differentiation (right), other expression changes are specific to the process.


If life seems like one inexorable process of specialization, take a closer look at the Dictyostelium slug. After forming from aggregated single cells, it is on its way to becoming a specialized fruiting body. But if its cells are dispersed and given nutrients they revert to their primitive, proliferative state. This dedifferentiation, say Mariko Katoh, Gad Shaulsky (Baylor College of Medicine, Houston, TX), and colleagues, is not a simple reversal of differentiation but a carefully regulated process. Similar regulation may ensure that dedifferentiating cells in a mammalian wound, for example, can fill in the wound without causing cancers or distorting the shape of the body part that was carefully crafted during development.

The group's claim is based on microarray results. Many of the transcriptional changes in dedifferentiating cells are a mirror image of those taking place in differentiating cells, but over 100 genes show changes specific to dedifferentiation. The set of genes is similar even when cells start dedifferentiating from different developmental stages.

One of the genes turned on during dedifferentiation encodes DhkA. Mutants lacking DhkA are slower to reinitiate cell division, but not DNA synthesis, during dedifferentiation. DhkA is a histidine kinase that, as part of a two-component system, is also required for the late differentiation event of sporulation. Shaulsky suggests that DhkA may be part of a checkpoint system in which completion of differentiation is contingent on accumulation of proteins (such as DhkA) necessary for dedifferentiation, thus ensuring that development is reversible. ▪


Katoh, M., et al.
Proc. Natl. Acad. Sci. USA.