Protocadherin-17 and -9 Function in Retinal Development

描述（由申请人提供）：本项目的长期目标是确定钙粘蛋白分子在脊椎动物视觉系统发育中的作用，特别强调视网膜。钙粘蛋白是一种重要的细胞粘附分子，与包括视觉系统在内的多种组织和器官的发育有关。原钙粘蛋白（protocadherins，pcdhs）基因突变可导致癫痫、智力低下和Usher综合征（视觉和/或听觉缺陷）等人类疾病。经典钙粘蛋白（如N-钙粘蛋白和R-钙粘蛋白，分别称为钙粘蛋白-2和钙粘蛋白-4）在脊椎动物视觉系统中的功能有广泛的信息，但对包括pcdhs在内的其他钙粘蛋白在视网膜发育中的功能知之甚少，并且没有关于pcdh 17和pcdh 9在脊椎动物视觉系统发育中的功能的公开报道。最近，我们以斑马鱼为模式生物，检测了pcdh 17和pcdh 9在发育中视觉系统中的表达，并开始研究pcdh 17在斑马鱼视网膜发育中的作用。本提案的具体目标是：1.以检验视网膜细胞的分化需要pcDH 17功能的假设;和2.以检验pcdh 9参与RGCs分化和寻路的假设。本项目将采用morpholino反义寡核苷酸技术、pcdh过表达、蛋白质组学、DNA微阵列等技术研究pcdh在视网膜发育中的作用。拟议的研究旨在揭示脊椎动物视网膜细胞发育的潜在机制，可能会为受伤或先天性缺陷的人类视网膜和视神经组织的治疗提供见解。 拟议的研究将发生在一个部门，有一个证明承诺本科研究人员的发展。我们建议加强和深化本科生的研究经验，并扩大接触他们的研究经验。我们将显着提高动手研究经验的学生参加细胞生理学，发育生物学，神经生物学和脊椎动物胚胎学的实验室组成部分（通过他们参与拟议的实验方面）。我们还将征求学生的建议，申请暑期奖学金，在那里他们可以追求自己的原创研究（围绕本提案中的主题）。然后，这些学生将在当地或地区本科生和研究生的研究座谈会上向其他本科生展示他们的研究。 公共卫生相关性：拟议的研究旨在揭示脊椎动物视网膜细胞分化的潜在机制，可能为受伤或先天性缺陷的人类视网膜和视神经组织的治疗提供见解。

DESCRIPTION (provided by applicant): The long-term objectives of this project are to determine the roles of cadherin molecules in the development of vertebrate visual system, with special emphasis on the retina. Cadherins are important cell adhesion molecules that have been implicated in the development of a variety of tissues and organs including the visual system. Mutations in protocadherins (pcdhs) cause humans diseases including epilepsy, mental retardation and Usher syndrome (visual and/or auditory defects). There is extensive information on function of classic cadherins (e.g. N-cadherin and R- cadherin, also called cadherin-2 and cadherin-4, respectively) in the vertebrate visual system, but little is known about other cadherins including the pcdhs function in retinal development, and there is no published reports on pcdh17 and pcdh9 function in the development of the vertebrate visual system. Using zebrafish as our model organism, we recently examined pcdh17 and pcdh9 expression in developing visual system and have begun to study the role of pcdh17 in zebrafish retinal development. The specific aims of the current proposal are: 1. to test the hypothesis that differentiation of retinal cells requires pcdh17 function; and 2. to test the hypothesis that pcdh9 is involved in RGCs differentiation and pathfinding. A variety of techniques including morpholino antisense oligonucleotides technique, pcdh overexpression, proteomics, DNA microarray, will be employed in the project to study pcdhs function in retinal development. The proposed studies, designed to uncover mechanisms underlying vertebrate retinal cell development, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues. The proposed research will take place in a department that has a demonstrated commitment to the development of undergraduate researchers. We propose to strengthen and deepen the undergraduate research experience and to broaden the exposure to their research experience. We will significantly enhance hands-on research experience for students enrolled in the laboratory component of Cell Physiology, Developmental Biology, Neurobiology and Vertebrate Embryology (through their participating in aspects of the proposed experiments). We will also solicit proposals from students to apply for summer fellowships, where they can pursue their original research (centered on the themes in this proposal). These students will then present their research to other undergraduates at local or regional undergraduate and graduate students' research symposiums. PUBLIC HEALTH RELEVANCE: The proposed studies, designed to uncover mechanisms underlying vertebrate retinal cells differentiation, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues.