Liver organogenesis promoted by endothelial cells prior to vascular function

Liver organogenesis promoted by endothelial cells prior to vascular function
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DOI:
10.1126/science.1063889
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发表时间:
2001-10-19
期刊:
影响因子:
56.9
通讯作者:
Zaret, KS
Zaret, KS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Matsumoto, K;Yoshitomi, H;Zaret, KS

文献摘要

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内皮细胞和新生血管在促进器官形成中的胚胎作用先于血管功能尚不清楚。我们发现小鼠胚胎中的早期内皮细胞围绕着新指定的肝内胚层,并界定了肝芽生长的间充质结构域。在flk-1突变的胚胎,缺乏内皮细胞,肝特化发生,但肝形态发生之前,间充质入侵失败。我们开发了一种胚胎组织外植体系统,允许肝芽血管发生,并表明,在没有内皮细胞,或当后者被抑制,有一个选择性缺陷,在肝生长。我们的结论是,血管内皮细胞和新生血管的器官形成的最早阶段,血管功能之前是至关重要的。
The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the Liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.