Discovering and Understanding Regeneration Suppressors

Although some animals can regenerate extensive body parts, the underlying molecular programs remain only partly understood, hindering our ability to induce regeneration in animals with limited tissue repair capabilities, including humans. While the focus in the field has long been on genes that promote regeneration, our work in highly regenerative planarian flatworms reveals an opposing regulatory program: regeneration suppressors. These genes must be downregulated for regeneration to begin – analogous to how tumor suppressors need to be silenced for tumorigenesis – and they encode secreted proteins and extracellular matrix components broadly expressed in many differentiated cell types. We propose that their combined activities create a diffuse tissue microenvironment to restrict regeneration. This distributed repression can confer robustness: for the environment to become permissive, wound signal must propagate systemically and reduce suppressor levels throughout the body and across different cell types. In this talk, I will discuss our approach to identify these suppressors, the function of these genes in regulating regeneration speed, and the signaling circuitry that modulates their expression during the regeneration process. I will also address how variations in the regulation of regeneration suppressors may lead to the differences in regeneration competence across animals.
 

Bio: Bo Wang is an associate professor of bioengineering at Stanford University. His group integrates bioengineering, computational biology, and developmental biology to unravel the mechanisms of animal regeneration, with a focus on how different cell types coordinate to rebuild new tissues after injury. A complementary long-term goal is to elucidate how distinct cell types emerge through evolution and how they interact to generate the complexity of multicellular life.