Identifying Mechanisms for Stem Cell Regulation by Wound–induced Signals
Most animals are able to repair wounds and many can regenerate extensively, yet little is known about how wounding results in regeneration, or whether these mechanisms are similar across diverse animal species. We are particularly interested in the phenomenon of "whole–body" regeneration where animals can regenerate virtually any missing tissue, making whole animals from small fragments of tissue. Animals with this capacity often harbor populations of pluripotent stem cells, which presumably become activated to generate new tissue in response to signals from the wound. We seek to build a model for the gene networks that are initiated upon wounding and how they regulate stem cells during regeneration.
We use a novel approach that enables a mechanistic understanding of regeneration by studying highly regenerative species in an evolutionary context. Since essential biological pathways tend to be well preserved over the course of evolution, we explicitly study multiple species to focus on conserved, as opposed to lineage-specific, mechanisms of animal regeneration. Acoels and planarians are two highly regenerative animals that diverged 550 million years ago from a last common ancestor that also gave rise to the human lineage. We study the mechanisms of regeneration in Hofstenia miamia, an acoel that we recently developed as a new model organism for studying regeneration, and in Schmidtea mediterranea, the traditional planarian model system. We do this by taking in integrative approach with a broad range of techniques including transcriptional profiling, RNAi, and lineage tracing.