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

半索动物神经组织：从保守的分子模式产生神经系统多样性

• 批准号: 1656628
• 负责人: Christopher Lowe
• 金额: $ 72.6万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656628&HistoricalAwards=false
• 关键词: Hemichordate; neural; organization; generating; system; Hemichordate; neural; organization; generating; system

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.

脊椎动物神经系统的进化起源一直是生物学的长期难题。更好的理解需要对策略选择，密切相关的动物群体中神经发育进行比较检查。该项目将调查半色调神经系统的结构和功能，海洋蠕虫与脊椎动物密切相关，但神经系统的组织原理完全不同。在脊椎动物和半色调之间的神经组织中特殊使用了总解剖学差异，研究人员将测试（尽管存在这些差异）是否（尽管存在这些差异）在至少某些分子信号中是否有密切相似性，这些分子信号指定了特定的神经细胞组的组织和连接。预计这些研究将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厚的进化前体，并且随着脊椎动物脑组织变得更加复杂，脊椎动物的前体已在以后进行。最后，预计这项工作将为脊椎动物和无脊椎动物神经系统的分子机制的详细功能提供新的启示。该提议的广泛目的是对肠神经系统的神经系统进行全面的分子表征，以确定基本组织的基本组织原理。 先前已经详细描述了直接发育的Kowalevskii的早期外胚层分化的分子遗传程序。这些由与脊椎动物类似的A/P轴沿着A/P轴进行精美保存的相对结构域组成。这一发现导致了难题。当神经系统的组织如此不同时，外胚层A/P程序如何在Enteropneusts和脊椎动物之间如此保守？解决此问题的关键是更好地了解半色调神经系统的分子遗传相关性。该项目调查了在双遗嘱中已经鉴定出的保守的核心基因套件的表达，这些基因定义了重要的神经元亚群。转基因方法还将用于研究GABA能和多巴胺能神经元的形态和投影，并开始鉴定神经整合的潜在部位。最后，将在功能上操纵与脊椎动物脑组织者同源的局部外胚层信号转导，以调查他们正在调节哪些神经元组。