Jiang Ji-ying, Li Ai-dong, Yang Shu-xia, Hong Hua-rong, Song Hong-rui, Mei Yan, Zhou Hong-ying, Yang Hui-jun
Department of Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul;36(4):493-6.
To investigate the function of HNF4a and HNF6 during liver development.
The expression levels of HNF4alpha and HNF6 at E8, 9, 13, 15, 17, P1 and in adult mouse liver were detected by RT-PCR and in situ hybridization.
RT-PCR results showed that HNF4alpha first expressed at E9, the time of liver bud formation, and lasted through all gestation and existed in adult liver. In situ hybridization showed that the expression of HNF4alpha was detected at the cells of liver cords during various stages of mouse liver development, and there were still a few HNF4alpha positive hepatocytes in adult liver. The cells of bile duct plate and biliary epithelial cells, endothelial cells, hematopoietic cells of liver were negative for HNF4alpha. The expression of HNF6 mRNA was detected in the liver at E9, the time of liver formation onset. Then, HNF6 mRNA disappeared transiently at E13, but it appeared again at E15. Its expression lasted until adult. In situ hybridization studies showed that most liver cord cells were positive for HNF6 at E9 and E15. At E17 and P1, the expression levels of liver cord cells declined, and HNF6 strongly expressed in the cells of bile duct plate and biliary epithelial cells.
HNF4alpha could modulate the formation of liver bud, trigger the differentiation of hepatic stem cell towards hepatocytes, and keep the shape of hepatocytes. HNF6 might play a role at the onset of liver development, in the differentiation of hepatic stem cell towards biliary epithelial cells, and in maintaining the morphological characteristic of biliary epithelial cells.
研究肝细胞核因子4α(HNF4a)和肝细胞核因子6(HNF6)在肝脏发育过程中的作用。
采用逆转录聚合酶链反应(RT-PCR)和原位杂交技术检测HNF4α和HNF6在胚胎期第8、9、13、15、17天、出生后第1天(P1)及成年小鼠肝脏中的表达水平。
RT-PCR结果显示,HNF4α在胚胎期第9天(肝芽形成期)首次表达,贯穿整个妊娠期,并存在于成年肝脏中。原位杂交显示,在小鼠肝脏发育的各个阶段,肝索细胞中均可检测到HNF4α的表达,成年肝脏中仍有少量HNF4α阳性肝细胞。胆管板细胞、胆管上皮细胞、内皮细胞及肝脏造血细胞中HNF4α呈阴性。HNF6 mRNA在胚胎期第9天(肝脏开始形成时)的肝脏中即可检测到表达。然后,HNF6 mRNA在胚胎期第13天短暂消失,但在胚胎期第15天再次出现,其表达持续至成年。原位杂交研究显示,在胚胎期第9天和第15天,大多数肝索细胞HNF6呈阳性。在胚胎期第17天和出生后第1天,肝索细胞的表达水平下降,HNF6在胆管板细胞和胆管上皮细胞中强烈表达。
HNF4α可调控肝芽的形成,促使肝干细胞向肝细胞分化,并维持肝细胞形态。HNF6可能在肝脏发育起始阶段、肝干细胞向胆管上皮细胞分化过程及维持胆管上皮细胞形态特征方面发挥作用。