Despite striking differences in form and function, all limbs develop in embryos using similar fundamental processes, like producing an outgrowth from the body and placing structures such as fingers, feathers, or suckers at appropriate positions. Legs, wings, flippers and tentacles are just some examples of the diverse variety of animal limbs. These results suggest that cephalopod limbs evolved by parallel activation of a genetic program for appendage development that was present in the bilaterian common ancestor. Cuttlefish also show proximodistal regionalization of Hth, Exd, Dll, Dac, Sp8/9, and Wnt expression, which delineates arm and tentacle sucker fields.

Inhibition of Bmp2/4 dorsally caused ectopic expression of Notum, which marks the ventral sucker field, and ectopic sucker development. Bmp and Wnt signals, which establish dorsoventral polarity in vertebrate and arthropod limbs, are similarly polarized in cuttlefish. Posterior transplantation of Hedgehog-expressing cells induced mirror-image limb duplications. In cuttlefish limb buds, Hedgehog is expressed anteriorly. 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. Cephalopod mollusks evolved numerous anatomical novelties, including arms and tentacles, but little is known about the developmental mechanisms underlying cephalopod limb evolution.

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