Protocadherin-17 and -9 Function in Retinal Development

描述（由申请人提供）：该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（pcdhs）的突变导致人类疾病，包括癫痫、智力迟钝和Usher综合征（视觉和/或听觉缺陷）。经典钙粘蛋白（如N-cadherin和R- cadherin，也分别称为cadherin-2和cadherin-4）在脊椎动物视觉系统中的功能信息广泛，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，pcdh17和pcdh9在脊椎动物视觉系统发育中的功能尚未见报道。我们最近以斑马鱼为模型生物，检测了pcdh17和pcdh9在视觉系统发育中的表达，并开始研究pcdh17在斑马鱼视网膜发育中的作用。当前提案的具体目标是：1。为了验证视网膜细胞分化需要pcdh17功能的假设；和2。以验证pcdh9参与RGCs分化和寻路的假设。该项目将采用多种技术，包括morpholino反义寡核苷酸技术、pcdh过表达、蛋白质组学、DNA微阵列等，研究pcdh在视网膜发育中的功能。这些研究旨在揭示脊椎动物视网膜细胞发育的机制，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。拟议的研究将在一个对本科生研究人员的发展有明确承诺的部门进行。我们建议加强和深化本科生的研究经验，拓宽他们的研究经验。我们将显著提高学生在细胞生理学，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的实践研究经验（通过他们参与的拟议的实验方面）。我们也将征求学生申请暑期奖学金的建议，在那里他们可以继续他们的原创性研究（集中在本提案的主题）。然后，这些学生将在当地或区域本科生和研究生研究研讨会上向其他本科生展示他们的研究成果。

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.