摘要
神经管畸形的发生是由遗传因素与环境因素共同作用产生的。平面细胞极性途径(planar cell polarity,PCP)对脊椎动物神经胚形成非常重要。该途径基因的任何突变都可能导致神经管不能闭合,与人类的颅脊柱裂相似。但是,环境因素是否影响、如何影响PCP途径基因的表达到目前仍不清楚。目的研究维甲酸对胎鼠Vangl1及Vangl2基因表达的时空特征的影响。方法全反式维甲酸橄榄油混悬液按120mg/kg在BALB/C小鼠怀孕第9·5天(E9·5)(B组)或E10·5(C组)灌胃,A组仅用橄榄油灌胃。取E9·5、E10·5、E11·5、E13·5、E15·5、E17·5、E19·5胎鼠,Vangl1及Vangl2基因表达量采用逆转录酶PCR(RT-PCR)检测,其时空表达采用全胚胎原位杂交(WISH)检测。结果结果显示,正常情况下Vangl1及Vangl2基因在整个神经胚形成过程中都有强表达。而B组胎鼠从脑到后神经孔Vangl1及Vangl2基因表达显著下调。C组较复杂,二基因表达在全胚胎(从E11·5到E13·5)及神经管脊柱区(从E15·5到E19·5)显著下调并维持低表达,但在神经管的颅区(E15·5到E19·5)仅中度下调。结论:结果提示,维甲酸诱导的神经管畸形的发生与Vangl1及Vangl2基因转录子下调有关。
Background： Planar cell polarity （PCP） pathway genes are important for vertebrate neurulation. Mutation of any of these genes may result in an open neural tube equivalent to human defect craniorachischisis. But how, if exist, environmental factors influence the expression of PCP pathway genes is not clear to date. Objectives ： To investigate the efforts of retinoic acid on the spatio- temporal expression of Vangl1 and Vangl2 in mouse fetus. Methods： Single dose of 120 mg/kg body weight of all trans -retinoie acid suspended in olive oil was administered orally to pregnant BALB/C mice on embryonic day （E） 9. 5 （group 2, G2 ） or E10. 5 （group 3, G3 ） ; pure olive oil was administered to group 1 （ G1 ） mice as control. The expressions of Vangl1 and Vangl2 in fetuses were investigated by reverse transeriptase PCR （ RT - PCR） and their spatial and temporal expressions were detected by whole - mount in situ hybridization （WISH） on E9. 5, E10. 5, E11. 5, E13.5, E15.5, E17. 5 and E19. 5 respectively. Results： Vangl1 and Vangl2 were strongly expressed throughout neurulation in G1 embryos. Embryos of G2 exhibited a dramatic downregulation of Vangl1 and Vangl2 expression from cranial region to posterior neuropore. In contrast, both two transcripts in G3 embryos were sharply downregulated and weakly expressed in whole embryo from E11.5. to E13.5 and in the spinal region of neural tube from E15.5 to E19. 5, but moderately downregulated in the cranial region of neural tube from E15.5 to E19. 5. Conclusion： Vangl1 and Yangl2 transcripts downregulation are implicated in occurrence of mouse NTDs induced by retinoic acid.
出处
《中国优生与遗传杂志》
2008年第3期23-26,F0003,共5页
Chinese Journal of Birth Health & Heredity
基金
国家重点基础研究发展计划(973计划)资助项目(2005CB522507)~~
关键词
神经管缺陷
脊柱裂
颅脊柱裂
维甲酸
神经胚形成
Neural tube defects
Spina bifida
Cranioraehisehisis
Tretinoin
Neurulation
