Spatiotemporal expression and retinoic acid regulation of bone morphogenetic proteins 2, 4 and 16 in Senegalese sole

Abstract

Bone morphogenetic proteins (BMPs) are involved in various physiological processes from early life stages throughout adulthood. Specific characteristics of BMPs have been used to define different subfamilies and BMP2/4 subfamily (composed of BMP2 and BMP4) has been linked to osteogenesis and skeleton development. BMP16 was recently identified as a new member of the BMP2/4 subfamily and reported as a teleost fish-specific form. In this work, we collected a comprehensive set of ray-finned fish BMP2, BMP4 and BMP16 sequences and demonstrated, through its presence in Holostei, that BMP16 is not restricted to teleost fish genome. Comparative analysis of BMP2, BMP4 and BMP16 primary structures revealed that most of the residues required for protein stabilization, dimer formation, glycosylation and receptor binding are substantially conserved between the three proteins, suggesting that BMP16, BMP2 and BMP4 may share similar mechanisms of action. In contrast, comparative analysis of gene expression profiles during Senegalese sole development revealed differences in onset and extent of gene expression, indicating that BMP16, BMP2 and BMP4 may contribute to different developmental and physiological processes. High levels of transcripts in adult calcified tissues and the up-regulation of gene expression by retinoic acid, a known regulator of skeletal development, suggests that BMP16 shares with BMP2 and BMP4 a role in bone metabolism and skeletal development. This study provides new insights into the taxonomic distribution and the spatiotemporal expression of BMP16 gene, and suggests that it may share structural and functional similarities with other members of the BMP2/4 protein subfamily.