PT - JOURNAL ARTICLE AU - Oscar A. Tarazona AU - Davys H. Lopez AU - Leslie A. Slota AU - Martin J. Cohn TI - Evolution of limb development in cephalopod mollusks AID - 10.1101/379735 DP - 2018 Jan 01 TA - bioRxiv PG - 379735 4099 - http://biorxiv.org/content/early/2018/07/31/379735.short 4100 - http://biorxiv.org/content/early/2018/07/31/379735.full AB - Cephalopod mollusks evolved numerous anatomical innovations, including specialized arms and tentacles, but little is known about the developmental mechanisms underlying the evolution of cephalopod limbs. Here we show that all three axes of cuttlefish limbs are patterned by the same signaling networks that act in vertebrates and arthropods, although they evolved limbs independently. In cuttlefish limb buds, Hedgehog is expressed anteriorly. Posterior transplantation of Hedgehog-expressing cells induced mirror-image limb duplications. Bmp and Wnt signaling, which establishes dorsoventral polarity in vertebrate and arthropod limbs, is similarly polarized in cuttlefish. Inhibition of the dorsal Bmp signal caused ectopic expression of Notum, a ventral sucker field marker, and development of ectopic suckers. Cuttlefish limbs also show proximodistally regionalized expression of Htx, Exd, Dll, Dac, Sp8, and Wnt genes, which delineate arm and tentacle sucker fields. These results suggest that cephalopod limbs evolved by parallel activation of an ancient developmental genetic program that was present in the bilaterian common ancestor.