The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration
The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration
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DOI：
10.1016/j.ydbio.2007.09.013
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发表时间：
2007-11-15
影响因子：
2.7
通讯作者：
Lemaigre, Frederic P.
中科院分区：
文献类型：
--
作者：
Margagliotti, Sabrina;Clotman, Frederic;Lemaigre, Frederic P.
哺乳动物的肝脏发育是由腹侧前肠内胚层形成肝芽开始的。然后肝细胞增殖并侵入横隔间充质，并进一步分化产生肝细胞和胆管细胞。通过分析敲除转录因子肝细胞核因子-6（HNF-6）/Onecut-1（OC-1）和OC-2的小鼠，我们在这里表明，这些因子冗余地刺激肝芽周围基底层的降解，并促进肝细胞在横隔中的迁移。基因表达分析表明，HNF-6和OC-2属于一个由E-cadherin、thrombospondin-4和osteopontin组成的基因网络，通过控制成肝细胞的迁移和粘附来调节肝芽的扩张。这个网络在肝脏发育开始时运作，包含了研究肝癌发生的候选基因。(c)2007爱思唯尔公司All rights reserved.
Liver development in mammals is initiated by the formation of a hepatic bud from the ventral foregut endoderm. The hepatic cells then proliferate and invade the septum transversum mesenchyme, and further differentiate to give rise to hepatocytes and biliary cells. By analyzing mice that are knockout for the transcription factors Hepatocyte Nuclear Factor-6 (HNF-6)/Onecut-1 (OC-1) and OC-2, we show here that these factors redundantly stimulate the degradation of the basal lamina surrounding the liver bud and promote hepatoblast migration in the septum transversum. Gene expression analysis indicates that HNF-6 and OC-2 belong to a gene network comprising E-cadherin, thrombospondin-4 and osteopontin, which regulates liver bud expansion by controlling hepatoblast migration and adhesion. This network operating at the onset of liver development contains candidate genes for investigation of liver carcinogenesis. (c) 2007 Elsevier Inc. All rights reserved.