Znf804a基因在发育期鼠脑神经元的迁移、增殖及分化中的功能

Function of Znf804a in neuronal migration,proliferation and differentiation during mice brain development

目的:以小鼠为模型研究精神分裂症易感基因Znf804a在神经发育中的功能。方法:利用胚胎电转技术,将Znf804a的shRNA(shZnf804a)质粒及其对照质粒(pSUPER)电转进入E14.5的癌症研究所(ICR)小鼠脑室区,每种质粒电转3只,分别为敲低(knock down)Znf804a组和对照组,比较两组神经元在皮层板(CP)区的比例来评价神经元的迁移速度;比较两组神经元前体细胞形成神经球的直径来评估神经元增殖速度;比较体外培养神经元前体细胞中Nestin染色阳性神经元的比例检测神经元分化速度。结果:敲低Znf804a小鼠的神经元迁移到CP区的比例比对照组低(11.8%vs.75.4%,P<0.001);神经元前体细胞形成神经球的直径比对照组大(295μm vs.172μm,P<0.01);神经元前体细胞中,Nestin染色阳性的神经元比例比对照组高(31.5%vs.9.6%,P<0.01)。结论:敲低Znf804a小鼠神经元迁移速度和分化速度比对照组神经元慢,增殖速度比对照组神经元快,提示Znf804a在小鼠脑发育过程中发挥重要功能。

Objective： To explore the function of Znf804 a during brain development by using mouse model.Methods： The sh RNA of Znf804 a（ sh Znf804 a） and control（ p SUPER） plasmids were introduced into ventricular zone of ICR（ Institute of Cancer Research） mice at E14.5（ three mice in each group） by using in utero electroporation.The speed of migration was evaluated by comparing the proportions of neuron in cortical plate（ CP）zone.The proliferation speed was evaluated by comparing the diameters of neurospheres formed by neuron progenitor cells.The differentiation speed was evaluated by comparing the proportions of Nestin staining positive cells in neuron progenitor cells.Results： The proportion of neurons in CP zone was lower in sh Znf804 a group than in controls（ 11.8% vs.75.4%,P〈0.001）.The diameter of neurospheres formed by neuron progenitor cells was bigger in sh Znf804 a group than in controls（ 295 μm vs.172 μm,P〈0.01）.The proportion of Nest in staining positive cells in neuron progenitor cells was larger in sh Znf804 a group than in controls（ 31.5% vs.9.6%,P〈0.01）.Conclusion： It suggests that the migration speed of neurons in sh Znf804 a is lower than that in controls,the proliferation speed is higher than that in controls,and the differentiation speed is lower than that in controls.These results indicate that Znf804 a may play an important role in the development of mouse brain.