The researchers, based at University College London and the National Institute for Medical Research, have won the prize for their discovery of a single molecular cue that promotes limb regeneration in salamander.
The Association’s oldest prize, now supported by Affymetrix, the Newcomb Cleveland Prize annually recognizes the author or authors of an outstanding paper published in the Research Articles or Reports sections of the journal Science between June and the following May.
When a salamander’s limb is severed, a mound of stem cells called a “blastema” forms at the amputation site. This clump of cells is surprisingly autonomous and provided it is innervated and vascularised, the blastema will regenerate a new limb to match what has been lost, regardless of where it is grafted. The division of the limb blastemal cells depends on signals from regenerating nerve axons so that limb regeneration is coupled to nerve regeneration after amputation.
The team, led by Professor Jeremy Brockes, MRC Research Professor at UCL, were studying the problem of patterning: how the salamander was able to regenerate just what it needed to replace what had been lost - a hand for a hand, an arm for an arm. This is how they came to test a protein called nAG which was able to act as a ligand for another protein, PROD1 which is relevant to tissue patterning.
To the team’s surprise, they found that after expression of nAG in the limb stump this receptor-ligand interaction reproduced the two aspects crucial for limb regeneration: pattern formation and growth. This meant that in a limb which had been denervated, by severing the nerve at the base of the limb distant from the amputation site, this single protein, nAG, could substitute for the regenerating nerve axons, and support regeneration to the digit stage.
Professor Brockes says: “We think that the nAG protein provides a new focus for understanding the role of the nerve in limb regeneration and how tissue patterning is integrated with growth control. Of course, with no nervous connection to the spinal cord, the limb that is regenerated cannot function, and nerve dependence of regeneration may have evolved as a mechanism to ensure functional innervation of the regenerate.”
Professor Brockes thinks that there are many hurdles that inhibit limb regeneration from occurring in mammals. But he adds: “We will of course need to find a bio-engineered solution to replacing limbs or organs in man, but in doing so we should pay attention to what occurs in those animals that are most adept at this. We should try to build in properties like autonomy into the specification of the stem cells and for this it will be crucial to understand these mechanisms.”
The UCL team will share $25,000 in prize money, to be awarded along with a medal each at the AAAS Annual Meeting in Chicago, which begins on 11 February.
Professor Brockes said: “This is a prize for a paper and the five authors are very grateful to the AAAS for honouring it in this way. We also thank the persons unknown who nominated the paper for this award. ”