The scientists from the Koenig lab theorize that the network of genes they discovered in squid may not be important for creating specific organs, but they may be doing something more generic that is useful for certain developmental functions, including both limb and lens development. These other developmental functions could include precise gene expression that places the right types, numbers, and shapes of cells in the right place at the right time. Limbs and eye lenses, for instance, start out as a flat sheet of cells that becomes patterned into concentric circles, a bullseye-like design, and develops from there to their final forms.

“Our finding breaks down the idea that the network evolved solely for ‘limb outgrowth’ function, but rather serves a broader function for any sort of patterning requiring this concentric-circle-like motif, including limbs, lens, tooth growth, and potentially others we have yet to identify,” said Kyle J. McCulloch, a postdoctoral fellow in the Koenig lab and lead author on the study.

Researchers got a better idea of the role these genes play in squid eye development by manipulating a cellular path called the WNT signaling pathway. In fruit flies, it is the pathway known for igniting the genes that lead to limb development.

The researchers wondered how a group of genes important for leg development made the eye lens and what the WNT signaling pathway was doing in lens development. They ran the experiment on squid embryos and found that over-activating this pathway resulted in loss of the eye lens. This is what led the scientists to believe that differences in how WNT signaling acts on these genes may be important for how the squid controls gene expression in the limb versus the lens.

The lab plans to keep studying these genes and compare their function in lens development to their function in the development of other morphological features.

“Ultimately this work shows the power of studying diverse systems,” Koenig said. “It’s surprising that genes that we have studied so well in other model systems like fruit flies and vertebrates, and that we thought we understood their function together was to make legs, are used for this totally different organ in the squid. It changes how we think about what these canonical genes do in development. By looking across the diversity of life, we actually might understand what these genes are doing more accurately.”

This work was funded by the National Institutes of Health and the John Harvard Distinguished Science Fellowship.