New understanding of regeneration gained by Forsyth scientists

Planaria worms demonstrate how cells communicate and grow new tissues

Forsyth Institute research with the flatworm, planaria, offers new clues for understanding restoration of body structures. Researchers at The Forsyth Institute have discovered how the worm’s cells communicate to correctly repair and regenerate tissue. Forsyth scientists have found that gap-junction (microscopic tunnels directly linking neighboring cells) communication contributes to this signaling. This research, led by Dr. Michael Levin, underlies principles that can potentially offer insight into human regeneration.

The restoration of body structures following injury requires both an initiation of growth and an imposition of the correct morphology upon the regenerating tissue. Understanding this process is crucial for both the basic biology of pattern formation, and for developing novel biomedical approaches. Planaria have powerful regeneration capability that makes them ideal for studying this process. When the worms are cut in half, the bottom section of the worm grows a head and the upper section a tail. Scientists have suspected that the ability of previously adjacent cells (on either side of the cut) to adopt radically different fates, as is the case with planaria where the cells have to decide whether to build a head or a tail, could be due to long-range signaling, which allows the determination of position relative to – and the identity of – remaining tissue.

Michael Levin, PhD., Associate Member of the Staff, said, “This research has important implications for understanding the signaling necessary to build (or re-build) complex structures. By understanding how cells communicate through gap junctional channels we can gain a greater understanding of how we can possibly direct this process in tissues that don’t currently regenerate; this has clear applications towards induction of regeneration in biomedical settings.” Dr. Levin and his team ultimately hope to gain an understanding of how adult stem cells are controlled by gap-junctional communication (GJC). As reported in the November 15 issue of Developmental Biology, Dr. Levin’s research team cloned and characterized the expression of twelve members of the innexin gene family during planarian regeneration. Innexins are proteins which make up gap junctions, and their expression was detected throughout the worms and in regeneration blastemas, undifferentiated cells from which an organ or body part develops, consistent with a role in long-range signaling relevant to specification of blastema positional identity.

Dr. Levin and Taisaku Nogi closed down the gap junctions to determine the impact on regeneration. As a result, the planaria often grew back two heads rather than a head and tail. The loss of GJC function had a direct impact on the regeneration process; without this communication the planaria cells at the posterior end became re-specified and formed a normal head, complete with brain, eyes, etc.. This is an example of a high-level “master” control signal. “If we can learn how to send appropriate signals through gap junctions, we may be able to tell the system to make a complex structure as needed.” said Levin.

Michael Levin, PhD. is an Associate Member of the Staff in The Forsyth Institute Department of Cytokine Biology. Through experimental approaches and mathematical modeling, Dr. Levin and his team examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. The lab’s investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a biological system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior.