Cut off the leg of an insect, and not only will the insect survive, but the leg will also grow back after some time. Cut off the leg of a human, and they’ll bleed out without proper medical attention (alas for us). Ultimately, insects are able to accomplish this amazing feat because they retain the biological pathways required for cells to differentiate and reorganize at a wound site, which is required in order to regenerate entire limbs.

The processes involve the dedifferentiation and redifferentiation of cells; however, the exact nature of the process is largely a mystery. Fortunately, some light has recently been shed on the matter, as researchers at Okayama University identified key genes involved in the regenerative process of the two-spotted cricket, Gryllus bimaculatus.

The Genes Involved

Epigenetic changes are heritable changes in gene expression that do not derive from changes in the DNA sequence. These may involve other biochemical processes, such as the methylation or demethylation of histones—the proteins that compact DNA—which causes gene downregulation or upregulation respectively. They have also been implicated in regeneration.

Taking this information, researchers considered the genes Gb'E(z) and Gb'Utx, which are involved in histone methylation and demethylation, respectively. Researchers silenced these genes via RNA interference on G. bimaculatus and observed the results when the crickets’ legs were amputated. Crickets whose Gb'E(z) was silenced regenerated legs with an extra segment. On the other hand, crickets whose Gb’Utx was silenced regenerated legs with joint defects.

In other words, Gb'E(z) and Gb'Utx epigenetically regulated leg patterning genes involved in regeneration. Silencing the Gb'E(z) or Gb'Utx caused misexpression of leg patterning genes that led to inappropriate leg regeneration. Although the exact mechanisms involved in regeneration still remain elusive, the study provides a clear contribution to an understanding of the epigenetic regulation of gene expression during tissue regeneration.

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