Regulatory networks underlying lens development and evolution

镜片发展和演变的监管网络

• 批准号: BB/D018579/1
• 负责人: Sebastian Shimeld
• 金额: $ 75.06万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD018579%2F1
• 关键词: Regulatory; networks; underlying; lens; development

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.

你是如何阅读这篇课文的？一个答案是，从页面反射的光线正在进入你的眼睛，并在你的视网膜上形成一个图像。感受器细胞检测到这一点，并将信息传输到你的大脑。形成清晰图像的关键步骤是光线在视网膜上的聚焦，而晶状体是这一过程中必不可少的一部分。随着晶状体的老化，它们的这一能力降低，视力下降，而晶状体疾病，如白内障，严重影响视力。晶状体的透明度和折射光线的能力来自于被称为晶体蛋白的高浓度蛋白质，以及含有晶体蛋白的细胞的阵列排列。所有脊椎动物(除了一些穴居和地下物种)都有带透镜的眼睛和随之而来的成像视力。大多数无脊椎动物也有眼睛，包括与近亲关系最近的脊椎动物、文昌鱼和海鞘。然而，这些动物不像脊椎动物那样形成复杂的图像，也没有镜头。因此，脊椎动物的晶状体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准确视觉起源和相关捕食生活方式的预测要求之一。那么这种透镜是如何进化的呢？在这个项目中，我们打算从基因和发育的水平来研究这一点。这背后的理性是，由于动物身体是通过胚胎发育形成的，随着进化时间的推移，动物身体的变化反映了塑造它们的发育过程的变化。在眼睛方面，由于众多研究小组的持续研究，我们对控制眼睛发育的基因了解很多。令人着迷的是，这些基因与昆虫和蠕虫等远亲动物控制眼睛发育的基因有相似之处。晶状体也有一些相同的基因，但除此之外，它还有自己独特的特性，尤其是定义其特殊特性的晶体蛋白基因的表达。我们打算从两个方向来处理这个问题。首先，我们将利用已出版文献中的丰富信息，建立详细的晶状体发育和分化的描述性模型。这些模型将在网上以交互方式展示，允许其他研究人员查看、评估、利用和批评它们。他们将对眼睛和晶状体发育的基因网络进行描述。同时，我们将研究这种网络的保守方面是如何在现存最接近的脊椎动物之一--海鞘(一种英国海岸附近的常见物种)身上使用的。这个物种在晶状体进化发生之前就从脊椎动物中分离出来，但我们最近的工作表明，构建晶状体所需的构件已经到位，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，可以确定与晶状体进化相关的差异。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。该项目的结果将与三组人相关。首先，那些对晶状体形成的分子控制感兴趣的人将能够利用我们建立的网络；这接近临床环境，从那里眼病形成了许多以前晶状体研究的驱动力。其次，了解基因网络是如何进化的，对于任何有兴趣将从一个物种收集的数据应用到另一个物种，尤其是将模型系统数据转移到人类的人来说，都是相关的。第三，我们相信，许多人认为我们最宝贵的感觉--视觉--的起源具有广泛的内在利益。

项目成果

Parallel evolution of chordate cis-regulatory code for development.

• DOI: 10.1371/journal.pgen.1003904
• 发表时间: 2013-11
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Doglio L;Goode DK;Pelleri MC;Pauls S;Frabetti F;Shimeld SM;Vavouri T;Elgar G
• 通讯作者: Elgar G

Dissection of a Ciona regulatory element reveals complexity of cross-species enhancer activity.

• DOI: 10.1016/j.ydbio.2014.03.013
• 发表时间: 2014-06-15
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Chen, Wei-Chung;Pauls, Stefan;Bacha, Jamil;Elgar, Greg;Loose, Matthew;Shimeld, Sebastian M.
• 通讯作者: Shimeld, Sebastian M.

Chordate betagamma-crystallins and the evolutionary developmental biology of the vertebrate lens.

脊索动物β-晶体蛋白和脊椎动物晶状体的进化发育生物学。

• DOI: 10.1016/j.cbpb.2007.03.014
• 发表时间: 2007
• 期刊: Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology
• 作者: Riyahi K