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

• Published in: Scientific reports 2015-01, Vol.5 (1), p.8123-8123, Article 8123
• Main Authors: Ivanova, Anastasiya S., Shandarin, Igor N., Ermakova, Galina V., Minin, Andrey A., Tereshina, Maria B., Zaraisky, Andrey G.
• Format: Article
• Language: English
• Subjects: 13; 38/22; 38/23; 38/71; 38/77; 38/88; 631/136/142; 631/136/2435; 631/136/2441; 631/181/2806; 64; 64/114; 64/116; Amphibians; Amputation; Animal Fins - physiology; Animals; Antisense oligonucleotides; Apoptosis - drug effects; DNA, Complementary - genetics; Embryo, Nonmammalian - metabolism; Embryonic Development - genetics; Fins; Gene Expression Regulation, Developmental; Humanities and Social Sciences; In Situ Hybridization; In Situ Nick-End Labeling; Injections; Morpholinos - administration & dosage; Morpholinos - pharmacology; multidisciplinary; Polymerase Chain Reaction; Protein Biosynthesis; Protein Disulfide-Isomerases - genetics; Protein Disulfide-Isomerases - metabolism; Regeneration - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Thioredoxin; Time Factors; Vertebrates; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep08123

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.