A planarian regrows its head with two tools. The first is a supply of adult stem cells, called neoblasts, that can turn into any tissue in the body. The second is a chemical signal, the Wnt pathway, that tells those cells which end of the fragment should become a head. Switch that signal off at a wound and the worm builds a head there.
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The scale of the feat is hard to overstate. The species Schmidtea mediterranea can rebuild an entire animal from a fragment as small as 1/279th of the worm. Cut one in half and each half grows into a planarian of its own.
Where do the new cells come from?
Neoblasts are the only cells in a planarian’s body tissues that can divide. Every cell in a new head has to come out of them.
For a long time nobody knew whether each neoblast could make everything, or whether each kind of tissue had its own specialist cells. In 2011, Daniel Wagner and Irving Wang at MIT set out to settle it. They hit planarians with enough radiation to destroy almost all their dividing cells. A few survivors remained, and within a week each had built a cluster of copies spread through the body. Every cluster came from one cell, yet held nerve, muscle, gut and other tissue.
Then came the harder test. The pair moved a single surviving cell from a donor into an irradiated worm that was dying. The cell divided and made skin, gut, nerves, muscle, eyes and a mouth. Two weeks on, the host had fully regenerated, and its whole body matched the donor cell’s genes. The team called these cells c-Neoblasts and published the work in Science.
That is unusual for an adult animal. In most species, adult stem cells can only make the tissue they belong to. A blood stem cell makes blood cells and not neurons. Some of a planarian’s adult cells keep the range an embryo has.
How does the fragment know where to put the head?
Raw material is not enough. A fragment also has to know its front from its back, and planarians settle that with signalling.
A team writing in Nature Ecology & Evolution describes a network of position signals that steers what each neoblast becomes. Along the head-to-tail axis, the Wnt pathway does most of the work. Turning Wnt up at a wound is enough to specify a tail. Turning it down is enough to specify a head.
The same team found this pathway behind the failures too. They gathered more than 40 planarian species from field sites around the world and scored how well each regrew a head. Some species regenerate from almost any piece. Others manage it only from certain regions, and some barely regenerate at all. In the species where the researchers could block Wnt by genetic interference, blocking it cured every head defect they saw. The authors suggest a trade-off with egg-laying may drive the loss, but say their comparisons were not conclusive.
Which parts of the body join in?
More of the worm responds than the stem cells. In 2021, Blair Benham-Pyle and colleagues in Alejandro Sánchez Alvarado’s lab at the Stowers Institute read gene activity in nearly 300,000 single cells. They compared worms that could regenerate with worms that had lost the ability.
All three of the worm’s germ layers responded to the cut, the team reported in Nature Cell Biology. Tissue far from the wound joined in as well as tissue beside it. They found five cell types that briefly changed their output after amputation. Muscle helped set the body pattern, and the skin helped trigger early bursts of stem cell division.
The gut surprised them. A badly cut worm often cannot eat, so it has to build from what it already holds. Benham-Pyle said the intestine switches to scavenging dying cells and turning that material into new tissue.
Does the new head remember anything?
Possibly. At Tufts University, Tal Shomrat and Michael Levin trained worms of the species Dugesia japonica to link a rough floor with food. They then removed every bit of brain and let the heads grow back over two weeks.
The trained group still headed for the food more than a minute faster than the untrained group. Smithsonian reported that nobody could yet explain how. Memories might sit somewhere in the body, or the old training might have shaped how the new brain grew.
A new head, it seems, does not always arrive blank.
