In planarians, flatworms capable of regrowing an entire brain after injury, researchers found genes that separately control what type of neuron a new cell becomes and where in the body it integrates
In planarians, flatworms capable of regrowing an entire brain after injury, researchers found genes that separately control what type of neuron a new cell becomes and where in the body it integrates
Biologists at the University of Georgia identified the genes that govern regeneration of dopaminergic neurons in planarians, the same cell type whose loss drives the symptoms of Parkinson's disease. Out of 74 candidate genes knocked down one at a time, ten proved essential for new dopaminergic neurons to appear in correct numbers. Two of them function throughout the worm's body; four others act only within a single region of the nervous system.
Planarians are flatworms a couple of centimeters long whose bodies are filled with specialized stem cells that can become any tissue type. After injury, these cells regenerate any amputated part, including the brain, producing the correct number of neurons of the correct types in the correct locations. During embryonic development, neurons arise according to a body plan, in positions that are already specified. During regeneration, a cell appears at the wound site with no such plan and must 'decide' on its own what kind of neuron to become and where to integrate. Neurons in the human central nervous system have almost no regenerative capacity, which is why planarians serve as the model for studying this question.
On September 21, 2026, the journal Nature Communications published a study whose authors focused on dopaminergic neurons. Planarians have these neurons in all three of their nervous systems, and in humans these are the cells that die in Parkinson's disease. The team selected 74 genes active in dopaminergic neurons and silenced each one individually by RNA interference, a technique that temporarily shuts off a gene. Silencing ten of these genes markedly reduced the number of new dopaminergic neurons after regeneration.
Two genes, fli1-2 and irx-4/6, are required for dopaminergic neurons throughout the body (in the brain, the periphery, and the pharynx), controlling both the production of new cells and their survival. Four others acted in only one location: lmo1/3-1 and app-L1 in the brain, soxB1-2 in the periphery, foxA in the pharynx. Cell type and cell position in the body are determined by different gene sets.
By labeling dividing stem cells, the researchers tracked the order in which genes switch on: the cell-type gene activates several hours before the positional gene, but both turn on within the first hours after division, and silencing one set reduces the activity of the other. The two mechanisms operate nearly simultaneously.
The effect was also visible in behavior. Planarians normally right themselves quickly when placed ventral side up. After these genes were silenced, the worms righted themselves more slowly, and some stopped doing so entirely, consistent with dopamine deficiency in other animals.
"Poor regenerative capacity is not an inherent property of brains in general. It is a feature specific to humans," says study leader Rachel Roberts-Galbraith of the University of Georgia in a comment to GEN.
The same problem exists in cell therapies for humans: dopaminergic neurons transplanted into mice and primates mature into the correct type in fewer than 30% of cases over 6 to 12 weeks and often migrate to the wrong location. In April 2025, the first such transplants into people with Parkinson's disease began: Sloan Kettering used embryonic cells, Kyoto University used reprogrammed cells from the patients themselves. A year later, a similar trial, STEM-PD, showed that the cells engrafted but dopamine levels had not returned to normal in any of the eight participants. The authors propose applying the same principle of separate programming of cell type and position to human transplants.
"We have worked out the genetic recipe for making these cells in planarians. We hope this will help create dopaminergic neurons that can be transplanted into patients more effectively," Roberts-Galbraith adds.