【摘要】 目的探讨FGF8在神经胚形成和神经管缺陷(NTD)发生过程中的作用及其可能的分子调控机制。方法采用全胚胎原位杂交技术观察FGF8在胚胎神经胚形成中的表达;通过喂服过量的维甲酸(retinoicacid,RA)诱导NTD模型,观察NTD鼠胚FGF8和STAT3的表达变化。结果①在E8·75d整个鼠胚几乎没有FGF8的表达;到E9·5d、E10·5d,在前脑泡的前缘、脑峡部位和神经管的末端观察到较局限的紫蓝色阳性区域,但到E10·5d时,上述3个部位的染色较E9·5d减弱;E11·5d时阳性信号主要集中在中脑部位。②FGF8在NTD鼠胚的表达,E9·5d时脑峡部位的染色减弱,前脑泡的前缘和神经管的尾端染色略有减弱;E10·5d,脑峡部位染色加深,且范围扩大,前脑泡的前缘和神经管的尾端染色较正常减弱。③STAT3在NTD鼠胚的表达,E9·5d和E10·5d时,STAT3的表达较正常鼠胚明显减少,在前脑泡和中脑泡均无明显的STAT3mRNA表达的阳性信号。结论FGF8可能作为STAT3的上游分子,二者共同参与了神经管的关闭。更多还原

【Abstract】 Objective To investigate the roles and possible molecular mechanism of FGF8 in the neurulation and neural tube defect (NTD). Methods FGF8 mRNA expression during neurulation was detected using whole-mount embryo in situ hybridization, as well as the changes of FGF8 mRNA expression and STAT3 mRNA expression in NTD induced by retinoic acid (RA). Results ① FGF8 was hardly detected in the whole embryos at E8.75d, but at E9.5d, FGF8 mRNA expression was found at the most anterior border of prosencephalon, isthmus and the end of neural tube. At E10.5d, the decreased expression of FGF8 mRNA was still observed in the above-mentioned three regions. During the late stage of neurulation, FGF8 mRNA expression was only detected in the mesencephalon at E11.5d. ②In the NTD embryos, FGF8 mRNA expression in the isthmus was weaker than that of the control at E9.5d, as well as stronger and more extensive than that of normal embryos at E10.5d. The signal of FGF8 mRNA in the anterior border of prosencephalon and in the end of neural tube was slightly weaker than that of normal embryos. ③As compared with the normal embryos, the expression of STAT3 mRNA was dramatically decreased at E9.5d and E10.5d in NTD embryos and undetectable in the prosencephalon and mesencephalon. Conclusion FGF8 might activate STAT3 in the STAT pathway during neurulation, and both of them may be involved in the closure of neural tube.更多还原