Shared developmental mechanisms pattern the vertebrate gill arch and paired fin skeletons.

Here, we describe the molecular patterning of chondrichthyan branchial rays (gill rays) and reveal profound developmental similarities between gill rays and vertebrate appendages. Sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8) regulate the outgrowth and patterning of the chondrichthyan gill arch skeleton, in an interdependent manner similar to their roles in gnathostome paired appendages. Additionally, we demonstrate that paired appendages and branchial rays share other conserved developmental features, including Shh-mediated mirror-image duplications of the endoskeleton after exposure to retinoic acid, and Fgf8 expression by a pseudostratified distal epithelial ridge directing endoskeletal outgrowth. These data suggest that the skeletal patterning role of the retinoic acid/Shh/Fgf8 regulatory circuit has a deep evolutionary origin predating vertebrate paired appendages and may have functioned initially in patterning pharyngeal structures in a deuterostome ancestor of vertebrates.