The Role of Ephrins in Topographic Mappin of the Visual System

Ephrins 在视觉系统地形图中的作用

• 批准号: 7331012
• 负责人: Jason Triplett
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7331012
• 关键词: Alzheimer' s Disease; Anterior; Area; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Automobile Driving; Axon; Behavior; Brain; Cell surface; Class; Complex; Degenerative Disorder; Detection; Development; Disease; Dorsal; Ensure; Eph Family Receptors; EphA1 Receptor; Ephrin-A5; Ephrins; Generalized seizures; Genetic; Goals; Knock-out; Knockout Mice; Lateral; Lateral Geniculate Body; Lead; Learning; Ligands; Macular degeneration; Maps; Medial; Methods; Midbrain structure; Modeling; Molecular; Mus; Neuraxis; Neurons; Nose; Parkinson Disease; Pattern; Personality; Play; Process; Receptor Protein-Tyrosine Kinases; Regulation; Research; Retina; Role; Sensory; Signal Transduction; Skin; Somatosensory Cortex; Synapses; Testing; Thalamic structure; Vibrissae; Visual; Visual system structure; area striata; extrastriate visual cortex; in vivo; insight; mouse model; nervous system disorder; receptor; retinogeniculate; role model; sensory integration; somatosensory; superior colliculus Corpora quadrigemina; vision development; visual information; visual map

DESCRIPTION (provided by applicant): The long-term objective of our research is to elucidate the mechanisms of precise neuronal targeting during development of the central nervous system (CNS): Specifically, we hope to gain an understanding of the molecular mechanisms underlying the phenomenon of topographic mapping in the visual system. In the pursuit of this goal, we will learn a great deal about neuronal development, which will prove useful in the understanding of both developmental and degenerative neuronal disorders. We will investigate the role of the cell surface ligands ephrin-As and their receptors, EphAs, in the precise topographic mapping of the visual system. We hypothesize that regulation of EphA/ephrin-A interactions are important for proper neuronal targeting. To test this we have developed two specific aims. In Aim 1, we will develop conditional knockout mouse models to delete ephrin-As specifically from the retina, midbrain, or cortex of developing mice. By specifically deleting ephrin-As, we will distinguish between three proposed models for the role of ephrins in neuronal targeting. In Specific Aim 2, we will determine the role of ephrin-As in the integration of sensory information in the brain. Detection, processing, and integration of multiple sensory inputs are necessary for survival. We will test the hypothesis that ephrin-As play an important role in ensuring that visual and somatosensory information are in register in the mouse superior colliculus using axon tracing methods in ephrin-A knockout models. Understanding the role of ephrins in this process will lead to insights into the integration of sensory information in 'higher' cortical areas responsible for attention, planning, and personality. In this study, we propose to use genetic mouse models to achieve a better understanding of the precise development of the visual system and CMS. Understanding this process will have broad impact in the treatment of developmental neurological disorders, such as generalized seizures, attention deficit hyperactivity disorder, and autism, as well as degenerative disorders, such as macular degeneration, Alzheimer's disease, and Parkinson's disease.

描述（由申请人提供）：我们研究的长期目标是阐明中枢神经系统（CNS）发育过程中精确神经元靶向的机制：具体而言，我们希望了解视觉系统中地形图现象的分子机制。在追求这一目标的过程中，我们将学习大量关于神经元发育的知识，这将有助于理解发育性和退行性神经元疾病。我们将调查的作用，细胞表面配体ephrin-As和它们的受体，EphAs，在视觉系统的精确地形图。我们假设EphA/ephrin-A相互作用的调节对于适当的神经元靶向是重要的。为了验证这一点，我们制定了两个具体目标。在目标1中，我们将开发条件性敲除小鼠模型，以特异性地从发育小鼠的视网膜、中脑或皮质中删除ephrin-As。通过专门删除肝配蛋白-作为，我们将区分三个提出的模型肝配蛋白在神经元靶向的作用。在具体目标2中，我们将确定ephrin-As在大脑中感觉信息整合中的作用。多种感觉输入的检测、处理和整合是生存所必需的。我们将测试这一假设，即肝配蛋白-A发挥重要作用，确保视觉和体感信息登记在小鼠上级丘使用轴突追踪方法在肝配蛋白-A基因敲除模型。了解肝配蛋白在这一过程中的作用，将有助于深入了解负责注意力、计划和个性的“高级”皮层区域中感觉信息的整合。在这项研究中，我们建议使用遗传小鼠模型来更好地理解视觉系统和CMS的精确发育。了解这一过程将对治疗发育性神经障碍（如全身性癫痫发作、注意缺陷多动障碍和自闭症）以及退行性疾病（如黄斑变性、阿尔茨海默病和帕金森病）产生广泛影响。