Mechanisms of neurogenesis in a segmented polychaete

中枢神经系统是一个复杂的器官，其适当的功能对于协调运动、感知和对环境条件的反应至关重要，并与动物的生存密切相关。了解如此复杂的器官是如何发育的，这是动物生物学中的一个基本问题。关于神经发育的详细细胞和分子知识仅限于对两个主要双边分支--蜕皮虫和后口动物--的模型系统的研究。Capitella是一种节段性蠕虫，是第三个双边分支--Lophotrochozoans的成员。这个项目使用细胞、分子和发育方法来描述这个环节动物模型中中枢神经系统的发育。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，它的基因组已经完全测序。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。将确定小脑神经系统神经前体细胞的来源、规格、内化方式和有丝分裂活性。控制这些过程的分子机制将结合基因敲除、错误表达和药理学方法进行分析。该项目将提供中枢神经系统是如何在多毛类环节动物中产生的关键信息，填补了目前关于轮虫的知识空白，并对中枢神经系统的进化有了深入的了解。该项目的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感兴趣。此外，这项拟议的工作将完善和进一步研究Capitella模型中基因功能的方法。该项目将把培训与研究结合起来，并通过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。结果将通过同行评议的出版物、会议介绍和外联活动向当地社区传播。

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.