Principal Investigator Peter Reddien
How are animals capable of specifying missing tissue types to initiate correct regeneration programs? We have studied the head-versus-tail regeneration choice made at transverse wounds (regeneration polarity) as a paradigm for addressing this question. We discovered that RNAi of bcatenin-1 causes the striking phenotype of head regeneration in place of tails. bcatenin proteins mediate Wnt signaling, and we determined that a wound-induced Wnt expression program is required for regeneration polarity. We next determined that the regeneration polarity choice is mediated by selective feedback inhibition of Wnt signaling at anterior-facing wounds by the action of the gene notum (encoding a secreted hydrolase), such that wound-induced WNT1 is selectively active at posterior-facing wounds. We have also characterized roles of dorsal-ventral patterning factors in guiding regeneration decisions, such as bmp4 and admp. This work on regeneration polarity and taken together with comparison of our data to that from embryos in other species, suggests that posterior Wnt activation is a unifying principle in the formation of the primary body axis of animals. Furthermore, regeneration could in principle have involved re-scaling of tissue gradients involving autonomous attributes of the signaling circuitry involved. By contrast, our data suggest that wounds have active input in the initiation of appropriate regeneration programs by induction of signaling proteins that specify regional tissue identity.