Self-Assembled Eyes Made Simple

Yokishi Sasai and his collaborators have been studying how mouse embryonic stem cells can be encouraged to develop into organs, particularly eyes.  In a recent issue of the journal Nature, Eiraku et al. describe a way to culture these stem cells in a new medium, which allows the cells to develop into dynamic, three-dimensional shapes.

When Eiraku et al. encouraged the stem cells to express an eye-inducing gene (retinal homeobox, also called Rx), a surprising result occurred.  Little vesicles developed from the aggregate of stem cells, and each vesicle self-organized into a simple optic cup, which is the first step towards developing a complex eye in mice (and ourselves):

The reason this result is so surprising is that many scientists have thought that patterning a structure as complicated as the optic cup would require chemical cues from other parts of the developing head, or from the eye lens that normally develops in alongside the optic cup.

In this next image, you can see how the developing optic cup begins expressing different genes in different cells, Rx is expressed in the cells facing outward, while another well-known eye-inducing gene, Pax6, begins to be expressed in the cells towards the back:

The changes in gene expression correlate with changes in cell flexibility.  Cells towards the back (seen above in red) become more ridged, while cells facing outwards (in green) become more flexible. This allows the cells facing outwards to buckle in, creating a self-organized cup. 

There are some interesting evolutionary consequences to this study.  Some of the simplest animal eyes, such as the ones I study in the jellyfish Aurelia, are simple cup eyes that are structurally similar to the optic cups described above:

Aurelia does not have a head or a lens to induce development of the optic cup, so it is interesting to see that mouse stem cells can self-assemble optic cups without the help of other body parts. 

Do mouse optic cups develop in the same manner as jellyfish?  We do not know yet if Aurelia has the gene Rx, but a relative of Aurelia­—the sea anemone Nematostella—definitely does (Mazza et al. 2010).  Our lab also has evidence that the optic cups of Aurelia do express a gene similar to Pax6 as well.  Whether the complex eyes of mice are modifications of the simple cup eyes of animals like jellyfish is going to require more research, but it is an intriguing possibility.

Works Cited

Mazza ME, Pang K, Reitzel AM, Martindale MQ, & Finnerty JR (2010). A conserved cluster of three PRD-class homeobox genes (homeobrain, rx and orthopedia) in the Cnidaria and Protostomia. EvoDevo, 1 (1) PMID: 20849646

Mototsugu Eiraku, Nozomu Takata, Hiroki Ishibashi, Masako Kawada, Eriko Sakakura, Satoru Okuda, Kiyotoshi Sekiguchi, Taiji Adachi, Yoshiki Sasai. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature, 2011; 472 (7341): 51 DOI: 10.1038/nature09941