CAREER: Factors Regulating Dendritic Arborization in the Xenopus Visual System

摘要神经元树突的构筑深刻影响其接收和传递突触信息的能力，并决定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对于了解单个神经元如何将自己连接到复杂的网络中是至关重要的。在当前职业奖项的背景下，Lom博士将使用正在开发的非洲爪哇视网膜顶盖投射来研究局部视网膜信号和靶点衍生的顶盖信号如何在体内和体外塑造非洲爪哇视网膜神经节细胞(RGC)树突状树突的早期形态发生。Lom博士将研究三个重要的树突状分化信号(BDNF、Activity和Fgf)如何将树枝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/或目标环境，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树枝。罗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项目。所有的实验问题和方法将完全融入本科研究培养计划，为本科生提供新的从事原创性研究的机会。认识到当学生将自己投入到真正的科学实践中时，他们学习得最好，这项提案中描绘的研究将通过三个项目为学生提供机会，就树突发育问题开展更广泛的独立研究项目：全职暑期工作，注册独立研究课程学分，以及注册发展神经生物学，这是一门独特的研究密集型小组调查课程。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，当地的高中生物教师也将在Lom博士的实验室担任暑期研究助理。通过亲身体验研究，高中教师将更好地熟练地在课堂上融入基于探究的实验。这项拟议研究的性质鼓励教师将他们的数据直接交到学生手中。高中生将分析树枝的形态，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，本科生和高中教师都将直接体验科学实践，因为他们有助于我们理解塑造树枝乔木发展的因素。

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.