Hemichordate neural organization: generating neural system diversity from conserved molecular patterning

脊椎动物神经系统的进化起源一直是生物学中的一个长期难题。更好的理解需要在战略选择，密切相关的动物群体的神经发育的比较检查。本项目将研究半索动物神经系统的结构和功能，半索动物是与脊椎动物密切相关的海洋蠕虫，但其神经系统的组织原理完全不同。特别利用脊椎动物和半索动物之间神经组织的总体解剖差异，研究人员将测试（尽管存在这些差异）是否至少在某些分子信号中存在密切的相似性，这些分子信号指定特定的神经细胞群是如何组织和连接的。这些研究有望为脊椎动物神经系统的组织和进化轨迹提供新的见解。这些实验还将使人们更清楚地了解脊椎动物神经系统的哪些元素在其他动物谱系中具有深刻的进化前体，以及哪些元素是后来随着脊椎动物大脑组织变得更加复杂而形成的。最后，这项工作有望揭示的详细功能的分子机制，模式的脊椎动物和无脊椎动物的神经systems.The广泛的目的，这项建议是进行一个全面的分子表征的神经系统的enteropneust hemicordate囊舌kowalevskii，以确定基本的组织原则。 直接发育的S. kowalevskii的结构域先前已被详细描述;这些结构域由与脊椎动物相似的沿着A/P轴的精确保守的相对结构域组成。这一发现引出了一个难题：当神经系统的组织如此不同时，肠外胚层的A/P程序在肠外胚层动物和脊椎动物之间如何保持得如此之好？解决这个问题的关键是更好地了解半索动物神经系统模式的分子遗传相关性。该项目研究了一套保守的核心基因的表达，这些基因已经在两侧对称中确定，定义了重要的神经元亚群。转基因方法也将用于研究GABA能和多巴胺能神经元的形态和投射，并开始鉴定神经整合的潜在位点。最后，局部外胚层信号中心同源的脊椎动物大脑组织者将进行功能操纵，以调查哪些神经元群体，他们正在调节。

The evolutionary origins of the vertebrate nervous system have been a long-standing puzzle in biology. A better understanding requires a comparative examination of neural development in strategically-chosen, closely-related animal groups. This project will investigate the structure and function of the nervous system of Hemichordates, marine worms closely related to vertebrates but with a nervous system that is completely different in its organizational principles. Making special use of the gross anatomical differences in neural organization between vertebrates and hemichordates, the investigators will test whether (in spite of these differences) there are close similarities in at least some of the molecular signals that specify how particular neural cell groups are organized and connected. These studies are expected to provide new insights into the organization and evolutionary trajectory of the vertebrate nervous system. The experiments will also lead to a clearer understanding of which elements of the vertebrate neural system have deep evolutionary precursors in other animal lineages, and which ones have come into being later on, as vertebrate brain organization became more complex. Finally, this work is expected to shed new light on the detailed function of the molecular mechanisms that pattern both vertebrate and invertebrate nervous systems.The broad aim of this proposal is to carry out a comprehensive molecular characterization of the nervous system of the enteropneust hemichordate Saccoglossus kowalevskii, in order to identify basic organizational principles. The molecular genetic programs of early ectoderm differentiation in the directly-developing S. kowalevskii have been previously described in detail; these consist of exquisitely-conserved relative domains along the A/P axis similar to those of vertebrates. This finding leads to a puzzle; how can the ectodermal A/P program be so well conserved between enteropneusts and vertebrates when the organization of the nervous system is so different? The key to addressing this issue is to better understand the molecular genetic correlates of nervous system patterning in hemichordates. This project investigates the expression of a conserved suite of core genes already identified in bilaterians that defines important neuronal sub-populations. Transgenic approaches will also be used to investigate the morphology and projections of GABAergic and dopaminergic neurons, and to begin to identify potential sites of neural integration. Finally, local ectodermal signaling centers homologous to vertebrate brain organizers will be functionally manipulated to investigate which neuronal groups they are regulating.