哺乳动物新皮质发育依赖于新生神经元的皮层定位并建立正确的突触连接，是行使脑功能的结构基础。异源三聚体G蛋白是细胞内重要的信号转导分子，由α，β和γ亚基组成，细胞内外信号激活导致Gα和Gβγ分离，在细胞不对称分裂、神经元电活动和神经递质释放等环节中发挥作用。Gβγ能够独立介导信号传递，还可能调节G蛋白与其它信号通路交互转导(cross talking) 。相对于Gα亚基，几种Gβ的生物学意义并不明确。结合近年研究进展和我们的工作基础显示，在新皮质发育过程表达丰度较高的Gβ2，调节新生神经元迁移。为此，我们制备了Gβ基因敲除鼠，在此基础上，将综合利用功能缺失、功能抑制和功能补偿等技术手段，深入研究Gβ2在新皮质神经前体细胞增殖与分化、新生神经元的迁移和成熟神经元的形态发生中的具体作用和调节机制。本研究将增进和完善G蛋白调控脑发育机理的认识，为正确理解脑发育相关疾病的发病机制提供科学依据。

Neural circuit in neocortex is the functional basis of mammalian brain, which relies on accurate neuron localization and correct synaptic connections. Heterotrimeric G protein, composed of α, β and γ subunits, is one of the most important intracellular signal transduction molecules. When activated by upstream signals, Gα separates from Gβγ to transduce signal to the downstream factors. In this way, Gα has been shown to regulate asymmetric cell division, neuronal electrical activity and neurotransmitter release. Gβγ is also an independent signal transducer and regulates cross talking between G protein and other signaling pathways. With respect to our knowledge of Gα, biological roles of several Gβ subtypes are still obscure. Evidence from recent publications and our own results showed Gβ2 was highly expressed in the developmental neocortex and regulated neuronal migration. In order to further investigate the roles of Gβ2 in the developmental stage, we have generated Gβ2 knockout mouse by using CRISPR technique. With this mouse model, we will systematically study the roles of Gβ2 in the proliferation and differentiationneural of precursor cell, neuronal migration and connection of neuronal synapse with loss-of-function, signaling inhibitor and functional rescue. The results from this proposal will enhance our understanding of G protein in neural development, and will be helpful to reveal the pathogenesis of neurological disorders.