Evolution of Eye Regression in Cavefish

9726561杰弗里这个项目的目的是研究脊椎动物眼睛退化的遗传基础。作为一个模型系统，我们将使用鱼类墨西哥海鞘(Astianax Micianus)。Astianax系统非常适合于研究眼睛退行性变，原因如下。首先，在上一个冰河时代，长着大眼睛的水面栖息的Astianax被隔离在洞穴中。这些居住在洞穴中的Astianax的后代后来失去了眼睛。已经收集了地表和洞穴栖息地的Astianax种群，目前可以在我的实验室进行研究。使用这些动物，我们将比较有眼睛和没有眼睛的动物的眼睛发育和退化。其次，在至少29个不同的洞穴中发现了盲目的Astianax，其中一些洞穴居民似乎已经失去了独立的眼睛。因此，我们可以在潜在不同的环境和进化条件下研究眼睛退化的遗传基础。第三，表层和穴居的海鞘很容易在实验室里养殖，很容易繁殖，是可互育的，而且表层鱼的眼睛结构与人类的相似。因此，Astianax可以作为一种方便的实验系统来帮助理解人眼的退化。这项提议有三个目标。首先，我们想要确定不同洞穴栖息地Astianax种群的眼睛退化的进化史。这将通过比较地表和各种洞穴种群的DNA序列来完成。这些结果将回答这样一个问题：在这些动物的进化史上，眼睛退化是只出现一次还是多次出现。第二，我们要在组织水平上确定眼睛退变的机制，即眼睛的哪些组织(晶状体、视网膜、角膜等)。实际上是堕落的。这将通过检查退化的眼睛组织中的细胞增殖和细胞死亡来完成。这些结果将使我们能够专注于在Vario us眼睛组织中发挥作用的特定基因。第三，我们想要确定与眼睛退化有关的基因。之前发现的眼睛基因的存在和功能将在地表和各种洞穴栖息的Astianax种群中进行研究。这一目标旨在建立眼睛退行性变的遗传学基础。这个项目的意义跨越了进化生物学、发育生物学和视觉系统功能等领域。在进化生物学中，这个项目意义重大，因为它将定义在上一个冰河时代可能发生过多次的进化变化的遗传基础。进化中的平行变化是由相同的还是不同的机制和基因控制的这个悬而未决的问题将会得到回答。在发育生物学中，这个项目意义重大，因为它将研究进化过程中潜在的发育变化机制。目前对器官系统的发育在进化过程中是如何改变的了解很少，我们希望填补这一空白。最后，这个项目在视觉系统功能方面具有重要意义，因为它解决了眼睛退化的遗传基础。冬虫夏草导致眼睛退化的一些机制和基因可能与人类视觉系统缺陷的机制和基因相同。

9726561 Jeffery The purpose of this project is to study the genetic basis of eye degeneration in a vertebrate animal. As a model system, we will use the fish Astyanax mexicanus. The Astyanax system is well suited for studying eye degeneration for the following reasons. First, during the last ice age, surface dwelling Astyanax, which have large eyes, were isolated in caves. The descendants of these cave-dwelling Astyanax subsequently lost their eyes. Both surface and cave dwelling Astyanax populations have been collected and are currently available for research in my laboratory. Using these animals we will compare eye development and degeneration in animals with and without eyes. Second, eyeless Astyanax are found in at least 29 different caves, and some of these cave dwelling populations appear to have lost their eyes independently. Therefore, we can study the genetic basis of eye degeneration under potentially different environmental and evolutionary conditions. Third, surface and cave dwelling Astyanax are easily cultured in the laboratory, breed readily, are inter-fertile, and the eye structure of the surface fish is similar to that found in humans. Thus, Astyanax can be used as a convenient experimental system to help understand human eye degeneration. This proposal has three objectives. First, we want to determine the evolutionary history of eye degeneration in different populations of cave dwelling Astyanax. This will be done by comparing DNA sequences of surface and various cave dwelling populations. The results will answer the question of whether eye degeneration appeared only once or many times during the evolutionary history of these animals. Second, we want to determine the mechanisms of eye degeneration at the tissue level, that is which eye tissues (lens, retina, cornea, etc.) actually degenerate. This will be done by examining cell proliferation and cell death in degenerating eye tissues. These results will allow us to focus on specific genes that function in vario us eye tissues. Third, we want to identify the genes involved in eye degeneration. The existence and function of previously identified eye genes will be studied in surface and various cave dwelling Astyanax populations. This objective is intended to establish the genetic basis of eye degeneration. The significance of this project spans the areas of evolutionary biology, developmental biology, and function of the visual system. In evolutionary biology, this project is significant because it will define the genetic basis of an evolutionary change which may have occurred multiple times during the last ice age. The open question of whether parallel changes in evolution are controlled by the same or different mechanisms and genes will be answered. In developmental biology, this project is significant because it will investigate the mechanisms underlying developmental changes during evolution. There is little current understanding of how development of organ systems is modified during evolution, and we expect to fill this void. Finally, this project is significant in regard to visual system function because it addresses the genetic basis of eye degeneration. Some of the mechanisms and genes underlying eye degeneration in Astyanax may be the same as those involved in visual system deficiencies in humans.