Latent Developmental Potential to Form Limb-Like Skeletal Structures in Zebrafish

Abstract

Changes in appendage structure underlie key transitions in vertebrate evolution. Addition of skeletal elements along the proximal-distal axis facilitated several critical transformations, including the fin-to-limb transition, which permitted generation of diverse modes of locomotion. Despite their importance in evolution, genetic changes that result in the establishment of new skeletal elements along this axis are unknown. Here, we identify zebrafish mutants that form novel bones in their pectoral fins with limb-like patterning. These new bones are integrated into musculature, form joints, and articulate with neighboring bones. Mutations in vav2 and waslb, members of a previously unrecognized appendage developmental pathway, cause this phenotype. We show that loss of Wasl in mouse limbs causes defects similar to those seen in Hoxa11 mutants. Concordantly, supernumerary bone formation in fins requires hoxa11, indicating developmental homology with the forearm. Our findings reveal a latent, limb-like pattern ability in fins that is activated by simple genetic perturbation.