The role of Frizzled receptors in the assembly of central synapses.

功能性大脑的形成需要适当的神经连接的组装。在发育过程中，神经细胞（神经元）延伸称为轴突的长过程，以寻找其目标，随后形成连接（突触）。突触包含两个主要组成部分，释放神经递质的突触前末梢和接受神经递质的突触后末梢（在目标中），以便将电脉冲从一个末梢（突触前）传递到另一个神经元（突触后末梢）。到达目标后，轴突接收刺激突触组装的信号。然而，神经细胞解释这些信号以启动参与神经递质释放的机器组装的机制仍然知之甚少。我们的实验室一直在研究Wnts的功能，Wnts是由突触靶点释放的分子，在哺乳动物大脑中形成神经连接。Wnt诱导关键分子聚集到轴突的特定区域，导致功能性突触的形成。然而，控制突触形成的机制仍然知之甚少。这个提议提出了神经元对信号做出反应的机制，以在正确的位置组装突触。使用神经元细胞培养物和突变小鼠，我们计划研究细胞外信号称为Wnts如何被接受细胞解释，以刺激特定位置突触的形成和维持。新的研究表明，在神经退行性疾病如帕金森病和阿尔茨海默病中观察到的神经细胞损失？突触的丧失会导致神经元分裂。因此，了解调节突触如何形成和维持的机制对于开发用于治疗和/或预防神经元变性的治疗策略至关重要。

The formation of a functional brain requires the assembly of appropriate nerve connections. During development, nerve cells (neurons) extend long processes called axons in search for their target to subsequently form connections (synapses). Synapses contain two main components, the presynaptic terminal that releases neurotransmitter and the postsynaptic terminal (in the target) that is receptive to neurotransmitters so that an electrical impulse is transmitted from one terminal (presynaptic) to another neurons (the postsynaptic terminal). After reaching their targets, axons receive signals that stimulate the assembly of synapses. However, the mechanisms by which nerve cells interpret these signals to initiate the assembly of the machinery involved in neurotransmitter release remains poorly understood. Our laboratory has been studying the function of Wnts, molecules released by synaptic targets, in the formation of nerve connections in the mammalian brain. Wnts induce the recruitment of key molecules to specific areas of the axon resulting in the formation of functional synapses. However, the mechanisms that control where synapses are formed remain poorly understood. This proposal addresses the mechanisms by which neurons respond to signals to assembly synapses at the right place. Using neuronal cell cultures and mutant mice, we plan to examine how extracellular signals called Wnts are interpreted by receptive cells to stimulate the formation and maintenance of synapses at specific locations. New studies suggest that neuronal cell loss observed in neurodegenerative diseases such as Parkinson and Alzheimer?s are trigged by the loss of synapses. Therefore, understanding the mechanisms that regulate how synapse are formed and maintained is crucial for the development of therapeutic strategies for the treatment and/or prevention of neuronal degeneration.