Liu Jian, Qi Jing, Zhu Jie, Zhang Lixia, Liang Yan, Ning Qin, Luo Xiaoping
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Neurogenet. 2008;22(3):167-79. doi: 10.1080/01677060802049605.
This study reports the effects of retinoic acid on the spatiotemporal expressions of Vangl1 and Vangl2 in mouse fetuses. A single dose of 120 mg/kg body weight of all-trans-retinoic acid suspended in olive oil was administered intragastrically to each pregnant BALB/C mice on embryonic day (E) 9.5 (group 1, G1) or E10.5 (group 2, G2); mice treated with pure olive oil on E9.5 or E10.5 served as control groups. The expression of Vangl1 and Vangl2 in fetuses was investigated by reverse transcriptase PCR (RT-PCR) and their spatial and temporal expression was detected by whole-mount in situ hybridization (WISH) on E10.5, E11.5, E13.5, E15.5, E17.5, and E19.5, respectively. The study indicated that the incidence of neural tube defects (NTDs) in live birth and craniofacial NTD rate were significantly higher in G1 (100% and 25.6%) than that in G2 (78.2% and 5.7%), both P < 0.01. Vangl1 and Vangl2 were strongly expressed throughout neurulation in embryos of control groups. G1 embryos exhibited a dramatic downregulation of Vangl1 and Vangl2 expression from cranial regions to posterior neuropore compared with the control group of G1 (all P < 0.01). In contrast, both transcripts in G2 embryos were significantly downregulated and weakly expressed in whole embryos on E11.5 and in the spinal region of the neural tube from E15.5 to E19.5, but moderately downregulated in the cranial region of the neural tube from E15.5 to E19.5 (all P < 0.01). In conclusion, Vangl1 and Vangl2 transcript downregulation might be implicated in the occurrence of mouse NTDs induced by retinoic acid.
本研究报告了视黄酸对小鼠胎儿中Vangl1和Vangl2时空表达的影响。在胚胎第9.5天（第1组，G1）或第10.5天（第2组，G2），对每只怀孕的BALB/C小鼠经胃内给予单剂量120 mg/kg体重悬浮于橄榄油中的全反式视黄酸；在第9.5天或第10.5天用纯橄榄油处理的小鼠作为对照组。通过逆转录聚合酶链反应（RT-PCR）研究胎儿中Vangl1和Vangl2的表达，并分别在胚胎第10.5天、第11.5天、第13.5天、第15.5天、第17.5天和第19.5天通过全胚胎原位杂交（WISH）检测它们的时空表达。研究表明，G1组活产中神经管缺陷（NTDs）的发生率和颅面部NTD率（分别为100%和25.6%）显著高于G2组（分别为78.2%和5.7%），两者P均<0.01。对照组胚胎在整个神经胚形成过程中Vangl1和Vangl2均强烈表达。与G1对照组相比，G1组胚胎从颅区到后神经孔Vangl1和Vangl2表达显著下调（所有P<0.01）。相反，G2组胚胎的两种转录本在第11.5天在整个胚胎中以及在第15.5天至第19.5天在神经管的脊髓区域显著下调且表达较弱，但在第15.5天至第19.5天在神经管的颅区中度下调（所有P<0.01）。总之，Vangl1和Vangl2转录本下调可能与视黄酸诱导的小鼠NTDs的发生有关。
