成熟的神经元具有高度极化的轴树突结构，保证了信息的单向传递，是构成功能性神经网络的基础。大脑皮层投射神经元的极性建立发生在新生神经元从多极形态向双极形态转换，确立引导突为树突雏形，尾随突为轴突雏形，经动态迁移和胞体移位定居皮层板。生理条件下，关于胞外导向因子在神经元极性发育过程的作用尚缺乏深入研究。结合近几年研究进展和我们的前期基础，推测脑室层高表达的Netrin-1通过局部激活跨膜受体结肠癌缺失蛋白（Deleted in Colorectal Cancer，DCC），促进神经元从多极形态向双极形态转换。胞外信号调节激酶1/2（Extracellular Signal-Related Kinase 1/2，ERK1/2）受DCC调节，是影响神经元极性和命运的关键内部因素。本立项主要通过体内电转技术以及细胞分子生物学手段，研究Netrin-1/DCC信号在神经元极性发育过程的作用及分子机制。

Neurons are highly polarized cells characterized by a long axon and multiple short dendrites. The polarization of axon and dendrites underlies the unidirectional flow of information transfer, which is essential for the establishment of functional circuits in the central nervous systerm. In development of cerebral cortex, after the final division, neurons transform from a multipolar to a bipolar shape with a leading process and a tail process which develop into dendrites and axons respectively and then migrate along radial glial fibres. Remarkble progress has been made in intracellular mechanism regulating neuronal polarity in the past three decades, however, the role of extracellular moleculars in neuronal polarity has not been fully understood. According to studies in our group, Netrin-1/DCC plays an important role in neuronal morphology transition and neuronal migration. We presume that Netrin-1 secreted from venticular zone and subventricular zone locally activates its membrane receptor DCC, which promotes neuronal transition from multipolar to bipolar. Extracellular signal-related kinase 1/2 (ERK1/2), key moleculars downstream of Netrin-1/DCC, play an important role in regulating neuronal polarity and neuronal fate. In this research, the expression pattern of Netrin-1 and DCC will be addressed and the involvement of Netrin-1/DCC in neuronal polarity, migration and fate detemination will be proved with the aid of in utero electroporation. In plus, we will put emphasis on the regulation of Netrin-1/DCC on ERK1/2 and investigate the coordination of neuronal polarization and neuronal fate.