Evolution of Axis Formation

0130375汉斯·博德在过去的20年里，人们对调控胚胎发育成有功能的动物的基因和分子机制有了大量的了解。 知识积累中最有趣的一个方面是，迄今为止研究的许多不同动物中，相似的基因和机制构成了相似的发育过程。 这些共同特点提出了一些重要问题。 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？ 在后生动物的进化过程中，一个特定基因的功能或基因通路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属于后生动物进化早期出现的动物群体的生物体中的功能。 其中最早的一个类群是刺胞动物，其成员包括水母、海葵和淡水水螅。 其中，水螅是特别有用的，因为发育过程是很好理解的。 拟议工作的总体目标是确定水螅中轴形成的基因和机制与脊椎动物和节肢动物相似的程度。 虽然水螅和所有刺胞动物都有一个轴，而两侧动物有两个轴[前-后和背-腹]，但许多已知参与脊椎动物和节肢动物轴形成的基因在水螅中起着类似的作用。需要解决的一个具体问题是涉及轴形成启动的基因和机制。 在脊椎动物中，一个被称为组织者的区域起着核心作用。 最近，水螅头的一个区域，即下体，已经被证明与这种脊椎动物的结构有明显的相似之处。 因此，本提案的重点是从水螅组织者中分离基因，确定它们的作用，并确定在何种程度上相同或相似的基因参与水螅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物。 这种方法非常成功，但缓慢而繁琐。 DNA阵列分析提供了一种手段，用于确定一个子集的基因中的几千个候选人的角色，在组织者活动的水螅。 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，这些基因中的每一个的作用将通过检查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测定来分析。所获得的信息将提供（a）更详细地了解水螅中的组织者，（B）更详细地了解这种结构的分子进化，（c）并可能鉴定通常可能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.