Evolution of Eye Regression in Cavefish

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0110275JefferyLittle is known about the remarkable evolutionary changes that have occurred in cave animals. This proposal continues Dr. Jeffery's research on the evolution of eye degeneration in Astyanax mexicanus, a teleost consisting of an eyed surface form (surface fish) and numerous conspecific eyeless cave forms (cavefish). Although cavefish lack eyes as adults, they form small eye primordia during embryogenesis, which later arrest in development and degenerate. In concert with eye degeneration, more elaborate feeding and gustatory systems have evolved in cavefish. His previous grant resulted in three new discoveries. First, he showed that eye degeneration has evolved independently in some cavefish populations. Second, he showed that lens apoptosis plays a major role in eye degeneration. Accordingly, the cavefish eye can be restored by transplantation of a surface fish lens primordium into the optic cup of a cavefish embryo. Third, he showed that Pax6, a gene required for eye development, is downregulated at the anterior midline in cavefish embryos. This discovery led to the hypothesis that cavefish exhibit enhanced midline signaling, the major focus of this proposal. He now plan to test this hypothesis and the possibility that degeneration of eyes and elaboration of feeding and gustatory organs have evolved repeatedly in cavefish due to hyperactive midline signaling during embryogenesis. The first objective is to determine whether cavefish embryos show hyperactive (hedgehog and/or nodal/TGFB) signaling at the anterior midline. Preliminary evidence shows that sonic hedgehog (Shh) gene expression is enhanced at the anterior midline in a single cavefish population. The second objective is to determine whether hyperactive midline signaling and Pax6 downregulation also occur in independently evolved cavefish populations. This will indicate whether the same or different developmental mechanisms have been changed during cavefish evolution. The third objective is to determine the effect of perturbing midline signaling on Pax6 expression and eye degeneration. He will test the possibility that surface fish and cavefish eye phenotypes are interchangeable by altering the levels of midline signaling gene expression in surface fish and cavefish embryos. Preliminary results show that changes in the level of Shh expression can phenocopy surface and cavefish. Time permitting, he will also determine whether eye degeneration involves changes in the organizer of cavefish embryos and whether there is a "developmental tradeoff" eye development and enhancement of feeding and gustatory systems, thus explaining evolutionary forces resulting in the cavefish phenotype. He expects the results of this investigation to provide new insights into the mechanisms underlying an evolutionary change in morphology.