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: 7674654
• 负责人: Jason Triplett
• 金额: $ 5.01万
• 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/7674654
• 关键词: Alzheimer' s Disease; Anterior; Area; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Automobile Driving; Axon; Behavior; Brain; Cell surface; Complex; Degenerative Disorder; Detection; Development; Disease; Dorsal; Ensure; Eph Family Receptors; 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; neuron development; 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开发过程（CNS）的精确神经元靶向的机制：具体来说，我们希望了解对视觉系统中地形图现象的分子机制的理解。为了实现这一目标，我们将了解有关神经元发展的大量知识，这将证明对理解发育和退化性神经元疾病有用。我们将研究细胞表面配体ephrin-AS及其受体的作用，例如，在视觉系统的精确地形图中。我们假设Epha/Ephrin-A相互作用的调节对于适当的神经元靶向很重要。为了测试这一点，我们开发了两个具体目标。在AIM 1中，我们将开发有条件的敲除小鼠模型，以从发育中的小鼠的视网膜，中脑或皮质中删除Ephrin-。通过特异性删除Ephrin-As，我们将区分三种提出的ephrins在神经元靶向中的作用的模型。在特定目标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，处理和整合对于生存是必需的。我们将检验以下假设：Ephrin-As在确保使用Ephrin-A敲除模型中的轴突示踪方法中在小鼠上丘中的视觉和体感信息发挥着重要作用。了解以弗林在此过程中的作用将导致对“高级”皮质区域中感官信息的整合的见解。在这项研究中，我们建议使用遗传小鼠模型，以更好地了解视觉系统和CM的精确发展。了解这一过程将对发育神经系统疾病的治疗产生广泛的影响，例如广泛性癫痫发作，注意力缺陷多动障碍和自闭症以及退化性疾病，例如黄斑变性，阿尔茨海默氏病和帕金森病。