Regenerative Research in Lower Animals: Planarians and Zebrafish

Many lower animals can regenerate from injuries that mammals cannot naturally heal - yet the fundamental components of their biology are much the same when considered at a high level. It's all cells and signalling molecules under the hood, and we're all sitting on branches of the same evolutionary tree. So it seems very plausible that there is something to be learned about regeneration from the biochemistries of species that can regrow lost limbs, completely heal heart injuries, or even grow half a body when needs must. Here is a small selection of research from the past week or so, illustrative of the work of a number of scientists investigating animals ranging from flatworms to salamanders.

Zebrafish Regrow Fins Using Multiple Cell Types, Not Identical Stem Cells

What does it take to regenerate a limb? Biologists have long thought that organ regeneration in animals like zebrafish and salamanders involved stem cells that can generate any tissue in the body. But new research suggests that multiple cell types are needed to regrow the complete organ, at least in zebrafish.


Limb regeneration has long captured people's imaginations.Traditionally, when people have looked at how a limb regenerates, they see a group of cells forming at the amputation site and the cells all look the same. So they've imagined that these cells have lost their identities and can become anything else. Our results show that this is not the case in the zebrafish fin. And there is mounting evidence that this is not the case in the salamander limb. ... This is evidence that we can't necessarily do regenerative medicine by plopping in generalized stem cells. The key may be to induce the cells that are already there to grow again. We need to understand and account for every cell lineage and then convince them to play ball together.

And just to show that there's no consistency whatsoever in nature, the story for the humble planarian appears to be quite the opposite.

Pluripotent adult stem cells power planarian regeneration

Ever since animals, such as lizards and starfish, were observed regenerating missing body parts, people have wondered where the new tissues come from. In the case of the planarian flatworm, Whitehead Institute researchers have determined that the source of this animal's extraordinary regenerative powers is a single, pluripotent cell type.


This is an animal that, through evolution, has already solved the regeneration problem. We're studying planarians to see how their regeneration process works. And, one day, we'll examine what are the key differences between what's possible in this animal and what's possible in a mouse or a person.

Heads or tails? Worm with abundant ability to regenerate relies on ancient gene to make decisions

This amazing ability of the planarian flatworm to regenerate its entire body from a small wedge of tissue has fascinated scientists since the late 1800s. The worms can regrow any missing cell or tissue - muscle, neurons, epidermis, eyes, even a new brain. Now Petersen and colleague Peter Reddien of the Massachusetts Institute of Technology (MIT) have discovered that an ancient and seldom-studied gene is critical for regeneration in these animals. The findings may have important ramifications for tissue regeneration and repair in humans.


In the paper, the authors describe how the gene notum acts at head-facing wounds as a dimmer switch to dampen the Wnt pathway and promote head regeneration. When the head or tail of a planarian is cut off, Wnt is activated. This Wnt activity turns on notum, but only at head-facing wounds. In a feedback loop, notum then turns Wnt down low enough that it can no longer prevent a head from forming. In tail-facing wounds, however, notum is not activated highly, a condition that promotes tail regrowth. (It takes the worm about a week to regrow a head or tail.)

The researchers are intrigued by this new role for notum. Like the Wnt signaling pathway, notum is highly conserved throughout species, from sea anenomes to fruit flies to humans, but little is known about its roles in biology. Because both notum and the Wnt signaling pathway are so evolutionarily ancient, their interaction in planarians may indicate a relationship that is important in other animals as well.

Wnt appears in a lot of published research into regeneration - it's clearly important in these processes, and the more that becomes known about the signalling systems of which it is a part, the better.


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