The tiny freshwater polyp Hydra is famous for its ability to regenerate: Cut the animal in two, and each half can reform a head with mouth and tentacles or a foot that anchors the animal to surfaces. Unlike other regenerating organisms, Hydra can do this by reshaping existing tissue rather than growing a large mass of new cells.

Researchers in the group of Charisios Tsiairis followed this process by measuring gene activity in individual cells over several days of regeneration. They found that cells first acquired features of nearby missing body regions and only later developed the gene-activity patterns of more distant structures, such as the head, tentacles or foot.

The work also shows that Wnt signaling — one of the molecular systems cells use to organize the body — changes during regeneration. Rather than sending a single instruction from the wound site to trigger regeneration, Wnt activity changes over time, helping guide cells through the steps needed to rebuild missing structures.

“The work suggests that cells need two kinds of information during regeneration: where they are in the body and where they are in the regeneration process,” Tsiairis says.

The findings also point to a general principle in regeneration, he adds. “Before missing structures can reappear, tissues may first need to recover the internal map that tells cells what to become.”