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Wnt/planar cell polarity signaling in synapse formation

突触形成中的 Wnt/平面细胞极性信号传导

基本信息

批准号：
8480101
负责人：
YIMIN ZOU
金额：
$ 23.25万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-18 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8480101
关键词：
Affect Alleles Angelman Syndrome Apical Behavioral Binding Proteins Biology Calcium Cell Adhesion Molecules Cell Polarity Cells Cerebellum Cognitive Complex Conflict (Psychology)Congenital Abnormality Data Dendritic Spines Development Diagnosis Disease Down Syndrome Electron Microscopy Embryo Ensure Epithelial Excitatory Synapse Fragile X Syndrome Frequencies Hippocampus (Brain)Inhibitory Synapse Knock-out Knockout Mice Knowledge Label Larva Lead Mediating Morphology Mus Mutant Strains Mice Nervous system structure Neuromuscular Junction Neurons Pathway interactions Play Postsynaptic Membrane Process Proteins Role Signal Pathway Signal Transduction Spinal Cord Staining method Stains Structure Synapses Synaptic Membranes Synaptic Vesicles Synaptophysin Synaptosomes Testing Tissues Wnt proteins autism spectrum disorder density disability in vivo mutant nervous system disorder neural circuit postsynaptic presynaptic protein complex research study synaptic function synaptogenesis transmission process

项目摘要

DESCRIPTION (provided by applicant): Neuronal synapses play pivotal roles in neural circuit functions. Abnormal synapse formation leads to numerous developmental diseases of the nervous system with cognitive and behavioral disabilities, including Down Syndrome, Angelman Syndrome, Fragile X Syndrome and Autism Spectrum Disorders. The mechanisms of how synapses form during development are poorly known. Understanding the basic mechanisms of synapse formation will be essential to understand the underpinnings of many birth defects in the nervous system for diagnosis and treatment. Several promising candidates for inducing synapse formation, such as the neuroligins and neurexins, are found not essential for synapse formation. Therefore, the question of synaptogenesis remains unsolved. Wnts have been shown to be able to regulate synapse formation in several embryonic neurons in hippocampus, cerebellum, spinal cord and the neuromuscular junction. Our preliminary results show that Wnt/planar cell polarity (PCP) signaling is required for excitatory synapse formation in dissociated hippocampal neuronal culture and in the neuromuscular junction in vivo. We propose to test the hypothesis that Wnt/PCP signaling is the central pathway, which directly assembles pre- and post-synaptic structures. PUBLIC HEALTH RELEVANCE: Abnormal synapse formation leads to numerous developmental diseases of the nervous system with cognitive and behavioral disabilities, including Down Syndrome, Angelman Syndrome, Fragile X Syndrome and Autism Spectrum Disorders. Understanding the basic mechanisms of synapse formation will be essential to understand the underpinnings of many birth defects in the nervous system for diagnosis and treatment. Several promising candidates for inducing synapse formation, such as the neuroligins and neurexins, are not essential for synapse formation. Therefore, the question of synaptogenesis remains unsolved. We propose to characterize the role and mechanisms of Wnt/PCP signaling in formation of excitatory synapses.

描述（由申请人提供）：神经元突触在神经回路功能中发挥着关键作用。突触形成异常会导致多种神经系统发育性疾病，伴有认知和行为障碍，包括唐氏综合症、天使综合症、脆性 X 综合症和自闭症谱系障碍。突触在发育过程中如何形成的机制知之甚少。了解突触形成的基本机制对于了解神经系统中许多出生缺陷的基础以进行诊断和治疗至关重要。一些有希望的诱导突触形成的候选物，例如神经连接蛋白和神经毒素，被发现对于突触形成并不是必需的。因此，突触发生的问题仍未解决。 Wnt 已被证明能够调节海马、小脑、脊髓和神经肌肉接头中多个胚胎神经元的突触形成。我们的初步结果表明，在分离的海马神经元培养物和体内神经肌肉接头中，Wnt/平面细胞极性（PCP）信号传导是兴奋性突触形成所必需的。我们建议检验 Wnt/PCP 信号传导是直接组装突触前和突触后结构的中央通路的假设。公共健康相关性：突触形成异常会导致多种神经系统发育性疾病，并伴有认知和行为障碍，包括唐氏综合症、天使综合症、脆性 X 综合症和自闭症谱系障碍。了解突触形成的基本机制对于了解神经系统中许多出生缺陷的基础以进行诊断和治疗至关重要。几种有前途的诱导突触形成的候选物，例如神经连接蛋白和神经毒素，对于突触形成来说并不是必需的。因此，突触发生的问题仍未解决。我们建议描述 Wnt/PCP 信号在兴奋性突触形成中的作用和机制。