Wnt/planar cell polarity signaling in synapse formation

描述（申请人提供）：神经元突触在神经回路功能中起着关键作用。异常的突触形成导致许多神经系统发育疾病与认知和行为障碍，包括唐氏综合症，天使综合征，脆性X综合征和自闭症谱系障碍。突触在发育过程中形成的机制尚不清楚。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诊断和治疗的基础至关重要。一些有希望诱导突触形成的候选物质，如神经素和神经素，被发现不是突触形成所必需的。因此，突触发生的问题仍未得到解决。wnt已被证明能够调节海马、小脑、脊髓和神经肌肉连接处几种胚胎神经元的突触形成。我们的初步结果表明，Wnt/平面细胞极性（PCP）信号是分离海马神经元培养和体内神经肌肉连接中兴奋性突触形成所必需的。我们建议验证Wnt/PCP信号是直接组装突触前和突触后结构的中心通路的假设。

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.