Eyes, Eyes, and more Eyes!

Developmental biology is all about context. It studies when, where, and to what extent are genes expressed in a developing organism. Molecular biology is all manipulation. It uses molecular scissors and glue to cut and paste pieces of genetic information to uncover a gene’s function. This fly is the classic example of how developmental biology and molecular biology synergize, illustrating that a single gene (which is normally expressed only in the developing eye) can direct eye formation at ectopic locations. Notice the eyes on the antennae and legs. You can’t see it from this angle, but this fly even even has some very small eyes on his wings and genitals! too many fly eyes

Using molecular biology techniques coupled with developmental biology knowledge, scientists showed that the eyes absent (eya) gene is both necessary and sufficient to form eyes, wherever it’s expressed! Nancy Bonini and her colleagues published their studies of eya in the journal Development in 1997. They co-opted a transcriptional control system from yeast (called the GAL4/UAS system) and stitched pieces of DNA from flies and yeast together to express eya in tissues where it’s normally silenced.

The fly pictured here is similar what was published in 1997. To get all those eyes in the all the wrong places, we mated virgin female flies carrying the UAS:eya transgene with male flies carrying the dpp:GAL4 transgene. When combined in the same fly, these transgenes trigger expression of eya in all of the imaginal discs (parts of the fly larvae that give rise to the adult appendages including antennae, wings and halteres, legs, and genitals).

The GAL4 gene, which encodes a transcription factor that binds to specific sequences called upstream activating sequence or UAS, is downstream of DNA sequences that normally elicit expression of the decapentaplegic (dpp) gene. Dpp is expressed in all imaginal discs (the parts of the fly larvae that give rise to the adult appendages including antennae, wings and halteres, legs, and genitals) and is required for patterning and proliferation.

When the genetic sequence of the eya gene was identified, and a closely related gene (homologue) was  identified in mammals, researchers were surprised to learn that eya could direct the cascade of events required for eye formation in organisms as distinct as flies and mice. Although this experiment was first performed in the late 1990s, it never gets old seeing how molecular biology can inform our understanding of the genetic basis of development.

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One comment

  1. How would I have ever known this? Thanks for the post!

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