Wnt/planar cell polarity signaling in synapse formation

描述（由申请人提供）：神经元突触在神经回路功能中起关键作用。异常突触形成导致许多神经系统发育疾病，具有认知和行为障碍，包括唐氏综合征、安格尔曼综合征、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诊断和治疗基础至关重要。几个有希望的候选人诱导突触形成，如神经连接素和neurexins，被发现不是必要的突触形成。因此，突触发生的问题仍然没有解决。Wnt已被证明能够调节海马、小脑、脊髓和神经肌肉接头中几种胚胎神经元的突触形成。我们的初步研究结果表明，Wnt/平面细胞极性（PCP）信号所需的兴奋性突触的形成在分离的海马神经元培养和在体内的神经肌肉接头。我们建议测试的假设，Wnt/PCP信号是中央通路，直接组装前和突触后结构。

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.