CAREER: Factors Regulating Dendritic Arborization in the Xenopus Visual System

摘要神经元树突的结构深刻地影响着神经元接收和传递突触信息的能力，并决定了神经元在突触回路中的作用。 因此，阐明控制树突发育的机制是理解单个神经元如何将自己连接成复杂网络的基础。 在本CAREER奖的背景下，Lom博士将使用正在开发的非洲爪蟾视网膜顶盖投射来研究局部视网膜信号和靶源性顶盖信号如何在体内和体外塑造非洲爪蟾视网膜神经节细胞（RGC）树突状细胞的早期形态发生。 Lom博士将研究三个重要的树突分化线索（BDNF，活性和FGF）如何将树枝化信号传递给发育中的RGC。 为此，Lom博士将在树突发育开始时改变局部和/或靶环境，并通过逆行荧光标记在体内和通过免疫染色在体外可视化RGC树突状乔木。 洛姆博士将在戴维森学院建立一个充满活力的发育神经生物学研究和培训计划。 所有的实验问题和方法将完全整合在本科研究培训计划，为本科生从事原创性研究提供新的机会。 认识到学生学习最好的时候，他们投资自己在做真实的科学的实践中，在这个建议中划定的研究将为学生提供机会，通过三个程序进行扩展的独立研究项目的树突发育的问题：全职暑期就业，在独立研究课程学分招生，并在发育神经生物学，一个独特的研究密集型群体调查课程招生。 由于积极参与科学研究的好处在高中科学课程中同样重要，当地高中生物教师也将被聘为洛姆博士实验室的暑期研究助理。 通过亲身体验研究，高中教师将能够更好地将基于探究的实验纳入课堂。 拟议研究的性质鼓励教师将他们的数据直接交给学生。 高中学生将分析树枝状乔木形态，从而体验研究过程的重要方面。 因此，通过在戴维森学院建立一个研究培训计划，本科生和高中教师将直接体验科学实践，因为他们有助于我们理解塑造树枝状乔木发展的因素。

Abstract The architecture of a neuron's dendritic arbor profoundly influences its ability to receive and transmit synaptic information and determine a neuron's role within synaptic circuitry. Elucidating the mechanisms that control dendritic development is therefore fundamental to understanding how individual neurons wire themselves into intricate networks. In the context of the present CAREER award Dr. Lom will use the developing Xenopus laevis retinotectal projection to investigate how both local retinal signals and target-derived tectal signals shape the early morphogenesis of Xenopus retinal ganglion-cell (RGC) dendritic arbors in vivo and in vitro. Dr. Lom will examine how three important dendritic differentiation cues (BDNF, activity, and FGF) transmit arborization signals to developing RGCs. To this end, Dr. Lom will alter local and/or target environments at the onset of dendritic development and visualize RGC dendritic arbors in vivo by retrograde fluorescence labeling and in vitro by immunostaining. Dr. Lom will establish a vibrant developmental neurobiology research and training program at Davidson College. All experimental questions and methods will be fully integrated in an undergraduate research-training program to provide new opportunities for undergraduates to engage in original research. Recognizing that students learn best when they invest themselves in the practice of doing real science, the research delineated in this proposal will provide opportunities for students to conduct extended independent research projects on questions of dendritic development through three programs: full-time summer employment, enrollment in Independent Research course credit, and enrollment in Developmental Neurobiology, a unique research-intensive group-investigation course. Because the benefits of active engagement in scientific research are equally important in the high-school science curriculum, local high-school biology teachers will also be employed in Dr. Lom's laboratory as summer research assistants. By experiencing research first-hand, high-school teachers will be better skilled to incorporate inquiry-based experimentation in their classrooms. The nature of the proposed research encourages teachers to place their data directly into the hands of their students. High-school students will analyze dendritic-arbor morphologies and thereby experience important aspects of the research process. Thus, by establishing a research-training program at Davidson College, both undergraduates and high-school teachers will directly experience the practice of science as they contribute to our understanding factors that shape the development of dendritic arbors.