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Agr  family includes three groups of genes,  Ag1 ,  Agr2  and  Agr3 , which encode the thioredoxin domain-containing secreted proteins and have been shown recently to participate in regeneration of the amputated body appendages in amphibians. By contrast, higher vertebrates have only  Agr2  and  Agr3 , but lack  Ag1 , and have low ability to regenerate the body appendages. Thus, one may hypothesize that loss of  Ag1  in evolution could be an important event that led to a decline of the regenerative capacity in higher vertebrates. To test this, we have studied now the expression and role of  Ag1  in the regeneration of fins of a representative of another large group of lower vertebrates, the fish  Danio rerio . As a result, we have demonstrated that amputation of the  Danio  fins, like amputation of the body appendages in amphibians, elicits an increase of  Ag1  expression in cells of the stump. Furthermore, down-regulation of  DAg1  by injections of Vivo-morpholino antisense oligonucleotides resulted in a retardation of the fin regeneration. These data are in a good agreement with the assumption that the loss of  Ag1  in higher vertebrates ancestors could lead to the reduction of the regenerative capacity in their modern descendants.

The secreted factor Ag1 missing in higher vertebrates regulates fins regeneration in Danio rerio