Regulatory networks underlying lens development and evolution

你是如何阅读这篇课文的？一个答案是，从页面反射的光线进入你的眼睛，并在视网膜上形成图像。受体细胞检测到这一点，并将信息传递到你的大脑。形成清晰图像的关键步骤是将光线聚焦在视网膜上，而透镜是这一过程中必不可少的一部分。随着晶状体老化，它们的视力下降，视力下降，而白内障等透镜疾病严重损害视力。晶状体的透明度和对光的吸收能力来自于高浓度的晶体蛋白质，以及含有晶体蛋白质的细胞的阵列状排列。所有的脊椎动物（除了一些穴居动物和地下物种）都有带晶状体的眼睛和随之而来的成像视觉。大多数无脊椎动物也有眼睛，包括脊椎动物最近的亲戚，文昌鱼和海蜇。然而，这些动物不像脊椎动物那样形成复杂的图像，也不形成透镜。因此，脊椎动物的透镜通常被认为是脊椎动物的发明，事实上，它的进化是祖先脊椎动物精确视觉和相关捕食生活方式起源的预测要求之一。那么，透镜是如何进化的呢？在这个项目中，我们打算在基因和发育水平上研究这一点。这背后的合理性是，由于动物身体是通过胚胎发育形成的，动物身体在进化过程中的变化反映了塑造它们的发育过程的变化。关于眼睛，由于许多研究小组正在进行的研究工作，我们对控制其发育的基因有了很多了解。有趣的是，这些基因与昆虫和蠕虫等远亲动物中控制眼睛发育的基因有相似之处。透镜也具有这些基因中的一些，但除此之外，它还具有自己独特的性质，尤其是晶体蛋白基因的表达，这些基因定义了它的特殊性质。我们打算从两个方向来处理这个问题。首先，我们将建立详细的描述模型的透镜的发展和分化，利用丰富的信息在出版的文献。这些模型将以交互方式显示在网络上，允许其他研究人员查看，评估，利用和批评它们。他们将形成眼睛和透镜发育的基因网络的描述。与此同时，我们将研究如何保守的方面，这个网络中使用的脊椎动物的近亲之一，海鞘海鞘（英国海岸周围的常见物种）。这个物种在透镜进化之前就从脊椎动物中分离出来了，但我们最近的工作表明，构建透镜所需的构件已经就位，包括晶体蛋白基因和控制其在感觉系统中精确表达的机制。进化的洞察力来自于对这两个网络的比较，而保守点，如晶体蛋白基因调控，提供了这一点的起点。然后可以确定与透镜演变相关的差异。从更广泛的角度来看，这让我们深入了解基因网络是如何进化的。该项目的成果将涉及三个群体。首先，那些对透镜形成的分子控制感兴趣的人将能够利用我们建立的网络;这接近了临床环境，眼科疾病已经形成了许多以前透镜研究的驱动力。其次，了解基因网络如何进化，对于任何有兴趣将从一个物种收集到的数据应用到另一个物种的人来说都是相关的，尤其是在将模型系统数据转移到人类方面。第三，我们相信，被许多人视为我们最宝贵的感官--视觉--的起源，具有广泛的内在利益。

How are you reading this text? One answer is that light reflected from the page is entering your eye and forming an image on your retina. Receptor cells detect this and transfer the information to your brain. A key step in forming a clear image is the focusing of light on the retina, and the lens is an essential part in this process. As lenses get old, they are less able to do this and visual acuity deteriorates, while lens diseases such as cataracts severely compromise vision. Lenses get their transparency and ability to refract light from high concentrations of proteins called crystallins, and the array-like arrangement of the cells that contain them. All vertebrates (with the exception of some cave-dwelling and subterranean species) have eyes with lenses and consequent image forming vision. Most invertebrates also have eyes, including the vertebrates nearest living relatives, amphioxus and sea squirts. However these animals do not form complex images as do vertebrates, and do not posses lenses. Consequently, the vertebrate lens is usually considered a vertebrate invention, and indeed its evolution is one of the predicted requirements for the origin of accurate vision and associated predatory lifestyle in ancestral vertebrates. How then did the lens evolve? In this project we intend to investigate this at the level of genes and development. The rational behind this that, since animal bodies form via embryonic development, changes in animal bodies over evolutionary time reflect changes in the developmental processes that sculpt them. With respect to the eye, we know a great deal about the genes that control its development, thanks to the ongoing research effort of numerous research groups. Fascinatingly, there are similarities between these genes and the genes that control eye development in distantly related animals such as insects and worms. The lens also shares some of these genes, but in addition has its own unique properties, not least the expression of the crystallin genes that define its special properties. We intend to approach this question from two directions. First we will build detailed descriptive models of lens development and differentiation, using the wealth of information in the published literature. These models will be interactively displayed on the web, allowing other researchers to view, evaluate, exploit and criticise them. They will form a description of the gene network underlying eye and lens development. In parallel we will investigate how conserved aspects of this network are used in one of the vertebrates closest living relatives, the sea squirt Ciona intestinalis (a common species around UK coasts). This species split from the vertebrate line before the evolution of the lens is thought to have occurred, but our recent work shows the building blocks needed to construct the lens were already in place, including the crystallin gene and the mechanisms controlling its precise expression in sensory systems. Evolutionary insight comes from comparing the two networks, and points of conservation, such as crystallin gene regulation, provide the starting point for this. Differences related to the lens evolution can then be determined. From a broader view point, this gives us insight into how gene networks evolve. The outcomes of this project will be relevant to three groups of people. First those interested in the molecular control of lens formation will be able to exploit the networks we established; this approaches the clinical environment, from which eye disease has formed the driving force for much previous lens research. Second, an understanding of how gene networks evolve is relevant to anyone interested in applying data gleaned from one species to another, and not least in the transfer of model systems data to humans. Third we believe the origin of what many would regard as our most precious sense, sight, is of broad intrinsic interest.