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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。
Objective To investigate the role of FGF8 in the process of neurogenesis and neural tube defects (NTD) and its potential molecular mechanisms. Methods Whole embryo in situ hybridization (FISH) was used to observe the expression of FGF8 in embryonic neurogenesis. NTD model was induced by excess retinoic acid (RA) and the expression of FGF8 and STAT3 in NTD mouse embryos was observed. Results ① There was almost no expression of FGF8 on the entire mouse embryo on E8 · 75d. By E5.5d and E10.5d, more limited purple-blue positive regions were observed at the anterior edge of the anterior segment of the brain, the brain isthmus and the end of the neural tube , But by the E10 · 5d, the staining of the above three sites was weaker than that of E9.5d; while the positive signals at E11 · 5d mainly concentrated in the midbrain. (2) The expression of FGF8 in NTD mouse embryos was weakened at E9.5d, while the leading edge of forebrain vesicles and the tail of neural tube were slightly weakened. On E10.5d, the brain isthmus was stained darker and wider, The anterior margin of the forebrain and the tail of the neural tube were weaker than normal. ③STAT3 expression in NTD mouse embryos, E9 · 5d and E10 · 5d, STAT3 expression was significantly decreased compared with normal mouse embryos, both in the anterior and middle cerebral cortex STAT3 mRNA expression was not positive signals. Conclusion FGF8 may be an upstream molecule of STAT3, both of which participate in the closing of neural tube.