Meeting Abstract

S5.7  Tuesday, Jan. 5  Evolution of mechanisms underlying limb regeneration in salamanders BROCKES, Jeremy P; UCL j.brockes@ucl.ac.uk

The most extensive regenerative ability among adult vertebrates is found in various species of salamander. In our work on the mechanism of limb regeneration we have identified a protein called Prod 1 which seems to be central to certain aspects of pattern formation, in particular proximodistal identity. We identified a secreted protein ligand for Prod 1 called nAG which seems to be central to the nerve dependence of regeneration. Prod 1 is a GPI anchored protein which signals to cells in part by interacting with the EGF receptor. The EGFR and nAG are familiar examples of well conserved ‘old’ proteins found in all vertebrates. By contrast, Prod 1 is a salamander specific protein which does not have a mammalian or zebra fish orthologue. It belongs to the 3 finger protein superfamily which takes up a versatile structure, a superfold, that can be accessed by many different postions in amino acid sequence space. 3FPs can be identified by the stereotyped spacing of 8 or 10 cys residues forming disulfide bonds. There are some striking examples of local evolutionary change which depend on the expansion and diversification of members of this family, for example the evolution of the venom apparatus in elapid snakes. I will review our data on Prod 1 which suggests a new view of salamander regeneration that emphasises such local evolutionary change. The salamander has ‘slotted in’ a new protein to interact with several old proteins and orchestrate their activities. It seemed unlikely to be the only such case, and this led us to identify another locally expanded group of 3FPs which also includes members that are involved in limb regeneration.