Brains, Brains Everywhere Flatworm gene that restricts brain tissue discovered

By Melissa Lee Phillips Neuroscience for Kids Consultant December 20, 2002 Planarians -- often called flatworms -- have an exceptional talent for regenerating. When a planarian is cut in half, each half can grow into a new whole worm! Even very small planarian pieces can develop into a perfectly organized whole. This amazing ability results from "totipotent" stem cells. These cells have the potential to develop into any type of cell in the body. Unlike most other animals, planarians have many of these special stem cells in their bodies. When a planarian is cut, its stem cells can form all of its body systems, including a well-organized central nervous system. Many neuroscientists hope that the study of planarians' regenerative abilities will lead to methods that can be used to regenerate human organs and tissues. A study published in Nature (October, 2002) reveals the importance of one particularly interesting planarian gene involved in regeneration. Scientists in Japan used a special technique called RNA interference to inactivate all copies of this gene. They then cut each worm in two and waited for the planarians to regenerate. The first few days of the planarians' regeneration seemed normal, but four or five days later, they began to develop brain-like structures slightly outside of the head region. After 15 days, the brain tissue expanded to the trunk and tail regions of the worms. The regenerated worms had brain tissue everywhere in their bodies! Their brain tissue was no longer only in their heads. The scientists named the inactivated gene nou-darake (ndk), which means "brains everywhere" in Japanese. The scientists think this strange result is centered around the structure of the protein that the gene ndk makes. Genes provide the directions for making proteins. The ndk protein (called NDK) is similar to proteins called fibroblast growth factor receptors. These receptors are used by another protein called fibroblast growth factor. The binding of the growth factor to its receptor promotes brain tissue development. Because NDK is so similar to this receptor, the growth factor can also attach to the NDK protein. When this happens, however, there are no instructions for brain tissue development. In a normal planarian head, fibroblast growth factors interact with their receptors in the head region to promote brain tissue development. The researchers also think that normal planarians have some "extra" growth factor present in the head that is soaked up by the NDK protein. When the ndk gene is inactivated, the NDK protein is missing. Therefore, there is nothing to soak up the extra growth factor in the head and some of it diffuses out to the rest of the body. It then binds with fibroblast growth factor receptors that are present in the trunk and tail, making brain tissue where it is not supposed to be. The result is a very odd looking planarian with brain tissue everywhere. Scientists believe that humans have a gene that is similar to the planarian ndk gene. Although the human gene may not be directly responsible for brain tissue placement as it is in flatworms, it is likely to be involved with nervous system development. More research will reveal the role of the ndk gene in humans.

For references and more information, see: Cebria, F., Kobayashi, C., Umesono, Y., Nakazawa, M., Mineta, K., Ikeo, K., Gojobori, T., Itoh, M., Taira, M., Sanchez Alvarado, A., and Agata, K., FGFR-related gene nou-darake restricts brain tissues to the head region of planarians, Nature, 419:620-624, 2002.