Mechanisms of neurogenesis in a segmented polychaete

中枢神经系统是一个复杂的器官，其正常功能对协调运动、感知和对环境条件的反应至关重要，与动物的生存密切相关。理解这样一个复杂的器官是如何发育的是动物生物学中的一个基本问题。神经发育的详细细胞和分子知识仅限于对三种主要双侧分支中两种的模型系统的研究，即外生动物和后口动物。小头虫是一种分节蠕虫，是第三种双边分支——光虫纲的成员。本项目采用细胞、分子和发育方法来描述这种环节动物模型中中枢神经系统的发育特征。Capitella为神经发生研究提供了几个优势，最值得注意的是它经历了胚胎和成年神经发生，它表现出强大的成年再生能力，其基因组已被完全测序。大脑发育的早期阶段将使用细胞标记方法、延时视频显微镜和基因沉默技术进行研究。小头神经系统神经祖细胞的起源、特征、内化模式和有丝分裂活性将被确定。控制这些过程的分子机制将使用敲低、错误表达和药理学方法的组合来分析。该项目将提供中枢神经系统如何在多毛类环节动物中产生的关键信息，填补目前在光面动物知识方面的空白，并对中枢神经系统的进化产生深入的了解。该项目的研究结果对包括神经生物学、发育生物学和进化生物学在内的几个生物学领域都很有意义。此外，所提出的工作将完善和进一步的研究方法的基因功能的模型Capitella。该项目将把培训与研究结合起来，并由PI承诺在实验室环境中进行培训。将鼓励妇女和太平洋岛民等代表性不足的群体参与国家的科学事业。研究结果将通过同行评议的出版物、会议发言和向当地社区宣传活动来传播。

The central nervous system is a complex organ whose proper function is critical for coordination of locomotion, sensing and responding to environmental conditions, and is closely tied to animal survival. Understanding how such a complex organ develops represents a fundamental question in animal biology. Detailed cellular and molecular knowledge of neural development is limited to studies in model systems of two of the three major bilaterian clades, the ecdysozoans and deuterostomes. Capitella is a segmented worm and member of the third bilaterian clade, the lophotrochozoans. This project employs cellular, molecular and developmental approaches to characterize development of the centralized nervous system in this annelid model. Capitella offers several advantages for neurogenic studies, most notably that it undergoes both embryonic and adult neurogenesis, it exhibits robust adult regeneration and its genome has been fully sequenced. Early stages of brain development will be investigated using cell labeling methods, time-lapse video microscopy, and gene silencing techniques. The origin, specification, mode of internalization, and mitotic activity of neural progenitor cells of the Capitella nervous system will be determined. Molecular mechanisms controlling these processes will be analyzed using a combination of knockdown, mis-expression and pharmacological approaches. The project will provide crucial information of how the central nervous system is generated in polychaete annelids, fill a current gap in knowledge of the lophotrochozoans, and yield insights into the evolution of the centralized nervous system.The results of this project are of interest to several fields of biology including neurobiology, developmental biology and evolutionary biology. In addition, the proposed work will refine and further methodology for studying gene function in the model Capitella. The project will integrate training with research and through a commitment by the PI to training in the laboratory environment. Women and underrepresented groups such as Pacific Islanders will be encouraged to participate in the nation's scientific enterprise. Results will be disseminated through peer-reviewed publications, conference presentations and outreach activities to the local community.