Hofstenia: distinct wound closure programs precede whole-body regeneration

In a worm that can regrow its entire body, a wound in the outer covering closes by contraction, whereas an incision through the pharynx prompts cells from two tissues to form temporary bridges

On August 11, Nature Communications published a study of the marine worm Hofstenia miamia, which can regenerate an entire body after amputation. When only the outer covering is damaged, its cells pull the wound edges together. If the incision also reaches the pharynx, cells from the two tissues first connect through long, temporary bridges.

The worm’s outer covering and the inner lining of its pharynx consist of dense cellular layers called epithelia. The researchers compared wounds that damaged one of these layers with wounds that affected both.

A transverse amputation below the pharynx damaged only the outer covering. Its edges moved toward the center as cells assembled actin filaments along the wound margin. These protein fibers help cells change shape and pull the gap closed. The head fragment then regrew a tail, while the tail fragment regrew a head. The outer covering closed in the same way in both fragments.

When the incision passed through both the outer layer and the pharynx, the sequence changed. Cells from the outer covering and the pharynx extended long, actin-based projections. These projections met above the wound and formed temporary bridges. Later, the cells in each layer reconnected with cells from the same layer.

To test whether the direction of the incision affected this response, the researchers cut through the pharynx both lengthwise and transversely. Bridges appeared in both cases. Together with the experiments on head and tail fragments, this result links the initial mode of wound closure to the cellular layers damaged by the incision.

The researchers then examined the forces that maintained the bridges. The anesthetic tricaine suppressed muscle contractions. Wounds involving one epithelium still closed at the same rate, but stable bridges did not form when two layers were damaged. Another drug, blebbistatin, inhibited myosin, a protein that works with actin to contract cellular structures. In wounds affecting two layers, only short projections remained instead of stable bridges. Both interventions specifically altered the bridging phase. This indicates that muscle contractions and the combined action of actin and myosin contribute to its mechanism.

Before a fragment can regrow a head or a tail, it must reconnect its damaged tissues. In this study, the cellular layers crossed by the incision determined how that repair proceeded. A single layer contracted to close the wound, whereas two layers first reconnected through temporary bridges.