Lamprey type II collagen and Sox9 reveal an ancient origin of the vertebrate collagenous skeleton

Abstract

Type II collagen is the major cartilage matrix protein in the jawed vertebrate skeleton. Lampreys and hagfishes, by contrast, are thought to have noncollagenous cartilage. This difference in skeletal structure has led to the hypothesis that the vertebrate common ancestor had a noncollagenous skeleton, with type II collagen becoming the predominant cartilage matrix protein after the divergence of jawless fish from the jawed vertebrates ≈500 million years ago. Here we report that lampreys have two type II collagen (Col2α1) genes that are expressed during development of the cartilaginous skeleton. We also demonstrate that the adult lamprey skeleton is rich in Col2α1 protein. Furthermore, we have isolated a lamprey orthologue of Sox9, a direct transcriptional regulator of Col2α1 in jawed vertebrates, and show that it is coexpressed with both Col2α1 genes during skeletal development. These results reveal that the genetic pathway for chondrogenesis in lampreys and gnathostomes is conserved through the activation of cartilage matrix molecules and suggest that a collagenous skeleton evolved surprisingly early in vertebrate evolution.