Development and evolution of the mammalian limb: adaptive diversification of nails, hooves, and claws

Paleontological evidence indicates that the evolutionary diversification of mammals early in the Cenozoic era was characterized by an adaptive radiati on of distal limb structures. Likewise, neontological data show that morpho logical variation in distal limb integumentary appendages (e.g., nails, hoo ves, and claws) can be observed not only among distantly related mammalian taxa but also among closely related species within the same clade. Comparat ive analysis of nail, claw, and hoof morphogenesis reveals relatively subtl e differences in mesenchymal and epithelial patterning underlying these adu lt differences in distal limb appendage morphology. Furthermore, studies of regulatory gene expression during vertebrate claw development demonstrate that many of the signaling molecules involved in patterning ectodermal deri vatives such as teeth, hair, and feathers are also involved in organizing m ammalian distal limb appendages. For example, Bmp4 signaling plays an impor tant role during the recruitment of mesenchymal cells into the condensation s forming the terminal phalanges, whereas Msx2 affects the length of nails and claws by suppressing proliferation of germinal epidermal cells. Evoluti onary changes in the form of distal integumentary appendages may therefore result from changes in gene expression during formation of mesenchymal cond ensations (Bmp4, posterior Hox genes), induction of the claw told and germi nal matrix (shh), and/or proliferation of epidermal cells in the claw matri x (Msx1, Msx2). The prevalence of convergences and parallelisms in nail and claw structure among mammals underscores the existence of multiple morphog enetic, pathways for evolutionary change in distal limb appendages.