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：具体来说，我们希望了解该现象背后的分子机制视觉系统中的地形图。在追求这一目标的过程中，我们将了解大量有关神经元发育的知识，这将有助于理解发育性和退行性神经元疾病。我们将研究细胞表面配体肝配蛋白-As 及其受体 EphAs 在视觉系统精确地形测绘中的作用。我们假设 EphA/ephrin-A 相互作用的调节对于正确的神经元靶向非常重要。为了测试这一点，我们制定了两个具体目标。在目标 1 中，我们将开发条件性基因敲除小鼠模型，专门从发育中的小鼠的视网膜、中脑或皮质中删除肝配蛋白-As。通过专门删除肝配蛋白-As，我们将区分三种提出的肝配蛋白在神经元靶向中的作用模型。在具体目标 2 中，我们将确定肝配蛋白-As 在大脑中感觉信息整合中的作用。多种感官输入的检测、处理和整合对于生存是必要的。我们将在肝配蛋白-A 敲除模型中使用轴突追踪方法来检验肝配蛋白-As 在确保视觉和体感信息在小鼠上丘中记录方面发挥重要作用的假设。了解肝配蛋白在此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”皮质区域的感觉信息整合。在这项研究中，我们建议使用遗传小鼠模型来更好地了解视觉系统和 CMS 的精确发育。了解这一过程将对发育性神经系统疾病（如全身性癫痫、注意力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）的治疗产生广泛影响。