von Willebrand factor D and EGF domains is an evolutionarily conserved and required feature of blastemas capable of multitissue appendage regeneration

Regenerative ability varies tremendously across species. A common feature of regeneration of appendages such as limbs, fins, antlers, and tails is the formation of a blastema-a transient structure that houses a pool of progenitor cells that can regenerate the missing tissue. We have identified the expression ofvon Willebrand factor D and EGF domains(vwde) as a common feature of blastemas capable of regenerating limbs and fins in a variety of highly regenerative species, including axolotl (Ambystoma mexicanum), lungfish (Lepidosiren paradoxa), andPolpyterus(Polypterus senegalus). Further,vwdeexpression is tightly linked to the ability to regenerate appendages inXenopus laevis. Functional experiments demonstrate a requirement forvwdein regeneration and indicate that Vwde is a potent growth factor in the blastema. These data identify a key role forvwdein regenerating blastemas and underscore the power of an evolutionarily informed approach for identifying conserved genetic components of regeneration.