Evolution of Eye Regression in Cavefish

0110275杰弗里对于洞穴动物发生的显著进化变化知之甚少。 这一提议延续了Jeffery博士对Astyanax mexicanus眼睛退化进化的研究，Astyanax mexicanus是一种硬骨鱼，由有眼的表面形式（表面鱼）和许多同种无眼的洞穴形式（洞穴鱼）组成。 虽然洞穴鱼在成年时没有眼睛，但它们在胚胎发育过程中形成了小眼睛原基，后来在发育过程中停止并退化。 与眼睛退化相一致的是，洞穴鱼进化出了更复杂的进食和味觉系统。 他之前的资助导致了三项新发现。 首先，他证明了眼睛退化在一些洞穴鱼类种群中是独立进化的。 其次，他指出透镜凋亡在眼睛退化中起主要作用。 因此，可以通过将表面鱼透镜原基移植到洞穴鱼胚胎的视杯中来恢复洞穴鱼眼睛。 第三，他发现眼睛发育所需的基因Pax 6在洞穴鱼胚胎的前中线下调。 这一发现导致了一个假设，即洞穴鱼表现出增强的中线信号，这是该提案的主要焦点。 他现在计划测试这一假设，以及由于胚胎发育期间中线信号过度活跃，眼睛退化和进食和味觉器官的发育在洞穴鱼中反复进化的可能性。 第一个目标是确定洞穴鱼胚胎是否在前中线显示过度活跃（刺猬和/或结节/TGFB）信号。 初步证据表明，音刺猬（Shh）基因的表达增强在前中线在一个单一的洞穴鱼类种群。 第二个目标是确定是否过度活跃的中线信号和Pax 6下调也发生在独立进化的洞穴鱼类种群。 这将表明是否相同或不同的发展机制已经改变在洞穴鱼类进化。 第三个目的是确定干扰中线信号传导对Pax 6表达和眼变性的影响。 他将通过改变水面鱼和洞穴鱼胚胎中线信号基因表达水平来测试水面鱼和洞穴鱼眼睛表型可互换的可能性。 初步结果表明Shh表达水平的变化可以表型化表面和洞穴鱼类。如果时间允许，他还将确定眼睛退化是否涉及洞穴鱼胚胎组织者的变化，以及是否存在“发育权衡”眼睛发育和增强摄食和味觉系统，从而解释导致洞穴鱼表型的进化力量。 他希望这项研究的结果能为形态学进化变化的机制提供新的见解。

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.