JEFFERY, W.R.; University of Maryland: The Lens as an Organizer of Eye Development and Evolution: A View from the Blind Cavefish, Astyanax

We study eye and visual development in eyed surface dwelling (surface fish) and eyeless cave dwelling (cavefish) forms of the teleost Astyanax mexicanus. Cavefish embryos form a small eye primordium, which arrests in development, undergoes lens apoptosis, and degenerates. The surface fish lens can rescue eye formation in cavefish after transplantation into the optic cup. Midline signaling by sonic hedgehog (Shh) mediates the small eye phenotype in cavefish by inducing Nk2.1a and Pax2, which in turn suppress Pax6 expression and activate lens apoptosis. In cavefish embryos, Shh expression is expanded laterally from the anterior midline, Nk2.1a and Pax2 expression is increased, and Pax6 expression is reduced in the optic primordia. To test the possibility that Shh controls cavefish eye degeneration, Shh mRNA was injected into surface fish eggs. In this experiment, a smaller eye was formed, the lens underwent apoptosis, and the eye degenerated, showing that enhanced Shh expression can phenocopy cavefish eye degeneration. Additional experiments shown that patterning of the sclera and other periocular structures is also dependent on the developing lens. Finally, we show that lens apoptosis, the key factor in eye degeneration and loss of vision in cavefish, is regulated by the chaperone hsp90-alpha, which is expressed in the developing cavefish but not the developing surface fish lens. A hypothesis will be presented in which the embryonic lens is featured as a global organizer of eye development and evolution.