Evolution of Axis Formation

汉斯·博德在过去的20年里，人们已经了解了许多关于基因和分子机制的知识，这些基因和分子机制调控着胚胎发育成正常动物的过程。积累知识最有趣的方面之一是，到目前为止所研究的许多不同动物中，相似的一组基因和机制构成了相似的发育过程。这些共同特征引发了许多重要问题。在动物进化过程中，这些基因是什么时候出现的？它们在最早的后生动物中就已经存在了吗？在后生动物进化过程中，某一特定基因或基因途径的功能在多大程度上是保守的？解决这些问题的一种方法是研究这些基因及其在后生动物进化过程中很早就出现的动物群中的生物体中的功能。Cnidaria是最早的类群之一，其成员包括水母、海葵和淡水九头蛇。其中，九头蛇特别有用，因为人们对其发育过程已经很清楚了。这项拟议工作的总体目标是确定九头蛇轴形成的基因和机制与已发现的脊椎动物和节肢动物相似的程度。尽管与双边动物的两个轴[前后轴和背腹轴]相比，九头蛇和所有蛇形动物只有一个轴，但在脊椎动物和节肢动物中，许多已知参与轴形成的基因在九头蛇中扮演着类似的角色。一个需要解决的具体问题涉及到启动轴形成的基因和机制。在脊椎动物中，一个被称为组织者的区域发挥着核心作用。最近，九头蛇头的一个区域，即后骨，被证明与这种脊椎动物的结构有明显的相似之处。因此，这项提议的重点是从九头蛇组织者中分离基因，确定它们的作用，并确定相同或相似的基因在多大程度上涉及九头蛇和脊椎动物组织者以及节肢动物组织区域。通常的方法是寻找在脊椎动物或果蝇的组织者活动中起作用的基因的同源基因。这种方法非常成功，但缓慢而乏味。DNA阵列分析提供了一种方法，可以从数千个候选基因中识别出在九头蛇组织者活动中扮演的角色。序列分析将揭示哪些是已知基因的同源物，哪些属于特定类别的基因，哪些是新基因。此后，将通过检测它们在组织者区域的发育和功能期间的表达模式以及使用功能分析来分析这些基因中的每一个的作用。所获得的信息将提供：(A)更详细地了解九头蛇中的组织者，(B)更详细地了解这种结构的分子进化，(C)以及可能识别通常参与组织者发育和活动的新基因。

0130375Hans Bode During the last 20 years a great deal has been learned about the genes and the molecular mechanisms that regulate the processes underlying the development of an embryo into a functioning animal. One of the most interesting aspects of the accumulating knowledge is that similar sets of genes and mechanisms underlie similar developmental processes in many of the diverse animals studied so far. These common features raise a number of important questions. When during animal evolution did these genes arise? Were they already present in the earliest metazoan? To what extent has the function of a particular gene, or pathway of genes been conserved throughout metazoan evolution? One approach to these issues is to study these genes and their functions in organisms that belong to groups of animals that arose very early during metazoan evolution. One of the earliest groups is the Cnidaria, whose members include jellyfish, sea anemones, and the freshwater hydra. Of these, hydra, is particularly useful since the developmental processes are well-understood. The overall aim of the proposed work is to determine the extent that the genes and mechanisms underlying axis formation in hydra are similar to those found vertebrates and arthropods. Though hydra, and all cnidarians, have a single axis compared to the two axes [anterior-posterior and dorsal-ventral] in bilaterians, a number of genes known to be involved in axis formation in vertebrates and arthropods play similar roles in hydra. A specific problem that needs to be addressed concerns the genes and mechanisms involved in the initiation of axis formation. In vertebrates, a region termed the organizer plays a central role. Recently, a region of the hydra head, the hypostome, has been shown to have clear similarities with this vertebrate structure. Thus, the focus of this proposal is to isolate genes from the hydra organizer, determine their roles, and determine to what extent the same or similar genes are involved in hydra and vertebrate organizers as well as arthropod organizing regions. The common approach is to look for homologues of genes that function in the organizer activity of a vertebtate or the fruit fly, Drosophila. This approach has been very successful but is slow and tedious. DNA array analysis provides a means for identifying a subset of genes among several thousand that are candidates for roles in organizer activity in hydra. Sequence analysis will reveal which are homologues of known genes, which belong to a specific class of gene and which are novel genes. Thereafter, the role of each of these genes will be analyzed by examining their expression patterns during the development and functioning of the organizer region as well as with the use of a functional assay. The information gained will provide (a) a more detailed understanding of the organizer in hydra, (b) a more detailed understanding of the molecular evolution of this structure, (c) and possibly the identification of novel genes that may generally be involved in organizer development and activity.