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Background Across the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Cephalopods have evolved a highly acute visual system with a cup-shaped retina and a novel refractive lens in the anterior, important for a number of sophisticated behaviors including predation, mating, and camouflage. Almost nothing is known about the molecular-genetics of lens development in the cephalopod. Results Here we identify the co-option of the canonical bilaterian limb patterning program during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factors  SP6-9/sp1 ,  Dlx/dll ,  Pbx/exd ,  Meis/hth , and a  Prdl  homolog in the squid  Doryteuthis pealeii , similar to expression required in  Drosophila  limb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing  Drosophila  limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. Conclusion This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate the co-option of the limb patterning program. Thus, our study suggests that this program could perform a more universal developmental function in radial patterning and highlights how canonical genetic programs are repurposed in novel structures.

Co-option of the limb patterning program in cephalopod eye development