Regeneration is a partial redeployment of the embryonic gene network

For more than a century, researchers have been trying to understand the relationship between embryogenesis and regeneration (Morgan 1901). A long-standing hypothesis is that biological processes originally used during embryogenesis are re-deployed during regeneration. In the past decade, we have begun to understand the relationships of genes and their organization into regulatory networks responsible for driving embryogenesis (Davidson et al. 2002; Röttinger et al. 2012) and regeneration (Srivastava et al. 2014; Lobo and Levin 2015; Rodius et al. 2016) in diverse taxa. Here, we compare these networks in the same species to investigate how regeneration re-uses genetic interactions originally set aside for embryonic development. Using a uniquely suited embryonic development and whole-body regeneration model, the sea anemone Nematostella vectensis, we show that at the transcriptomic level the regenerative program partially re-uses elements of the embryonic gene network in addition to a small cohort of genes that are only activated during regeneration. We further identified co-expression modules that are either i) highly conserved between these two developmental trajectories and involved in core biological processes or ii) regeneration specific modules that drive cellular events unique to regeneration. Finally, our functional validation reveals that apoptosis is a regeneration-specific process in Nematostella and is required for the initiation of the regeneration program. These results indicate that regeneration reactivates embryonic gene modules to accomplish basic cellular functions but deploys a novel gene network logic to activate the regenerative process.