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

Stephanie Neal, Kyle J. McCulloch, Francesca R. Napoli, Christina M. Daly, James H. Coleman, Kristen M. Koenig

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article number1
JournalBMC Biology
Issue number1
StatePublished - Dec 2022
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank the Koenig and Srivastava lab members for helpful discussions as well as Kevin Woods and the John Harvard Distinguished Science Fellows community for support. We would like to thank Jeffrey Gross, Alex Schier, Mansi Srivastava, Nick Bellono, and Andrew Murray for comments on the manuscript. We also thank the Marine Biological Labs, the Marine Resources Center, Owen Nichols, Ernie Eldredge, and Shannon Eldredge for assisting in the acquisition of embryos. We would also like to acknowledge the Harvard College undergraduates of LS50: Integrated Science Laboratory Course: Zach Alerte, Vlad Batagui, Eli Burnes, Stephen Casper, Chris Chen, Ahab Chopra, Ralph Estanboulieh, Lily Gao, Pedro Garcia, Saimun Habib, Harry Hager, Maxwell Ho, Charlie Horowitz, Ray Jiang, Prashanth Kumar, Truelian Lee, Arian Mansur, Matthew Mardo, Mark Theodore Meneses, Kendrick Nguyen, Francesco Rolando, Simon Schnabl, Taylor Shirtliff-Hinds, Sorscher Lincoln, William Stainier, Avi Swartz, David Szanto, Sophia Tang, Joey Toker, Analli Torres, Nina Uzoigwe, Rowen VonPlagenhoef, Evelyn Wong, Alexandra Zaloga, Maxwell Zhu.

Funding Information:
This work is supported by the Office of the NIH Director 1DP5OD023111-01, John Harvard Distinguished Science Fellowship to K.M.K.

Publisher Copyright:
© 2021, The Author(s).


  • Cephalopod
  • Dlx
  • Eye
  • Eye evolution, Lens
  • Limb patterning
  • Spiralia
  • Vision
  • Wnt

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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