Systematic analysis of cell signaling during planarian tissue regeneration, remodeling & homeostasis

Abstract

We have initiated a systematic effort to define the roles of highly conserved signaling pathways in the planarian Schmidtea mediterranea, an organism with astounding regenerative capabilities. Following amputation, freshwater planarians properly regenerate a head or tail from the resulting anterior or posterior wound. The mechanisms that differentiate anterior from posterior and direct the replacement of the appropriate missing body parts are unknown. We report that RNA interference (RNAi) of β‐catenin or dishevelled causes the regeneration of a head instead of a tail at posterior amputations. Conversely, RNAi of the β‐catenin antagonist adenomatous polyposis coli (APC) results in the regeneration of a tail at anterior wounds. The reversal of tissue identity is complete by both anatomical and molecular criteria, it can be observed as early as 12 hours post‐amputation, and it is independent of the angle or location of amputation. However, systematic silencing of known upstream components did not recapitulate these defects. The intracellular components of canonical Wnt signaling may therefore be regulated by an unconventional upstream mechanism in regenerating planarians. In addition, β‐catenin RNAi transforms the tail of uncut adult animals into a head. We suggest that β‐catenin is a molecular switch that specifies and maintains AP identity during planarian regeneration and homeostasis.K.A.G., F32GM082016, T32CA093247. J.C.R., European Molecular Biology Organization. A.S.A., HHMI Investigator and RO‐1 GM57260