Sakaguchi Takuya F, Sadler Kirsten C, Crosnier Cecile, Stainier Didier Y R
Department of Biochemistry and Biophysics, Program in Developmental Biology, University of California, San Francisco, California 94158, USA.
Curr Biol. 2008 Oct 28;18(20):1565-71. doi: 10.1016/j.cub.2008.08.065.
Emerging evidence indicates that paracrine signals from endothelial cells play a role in tissue differentiation and organ formation [1-3]. Here, we identify a novel role for endothelial cells in modulating hepatocyte polarization during liver organogenesis. We find that in zebrafish, the apical domain of the hepatocytes predicts the location of the intrahepatic biliary network. The refinement of hepatocyte polarization coincides with the invasion of endothelial cells into the liver, and these endothelial cells migrate along the maturing basal surface of the hepatocytes. Using genetic, pharmacological, and transplantation experiments, we provide evidence that endothelial cells influence the polarization of the adjacent hepatocytes. This influence of endothelial cells on hepatocytes is mediated at least in part by the cell-surface protein Heart of glass and contributes to the establishment of coordinately aligned hepatocyte apical membranes and evenly spaced intrahepatic conduits.
新出现的证据表明,内皮细胞的旁分泌信号在组织分化和器官形成中发挥作用[1-3]。在此,我们确定了内皮细胞在肝脏器官发生过程中调节肝细胞极化的新作用。我们发现在斑马鱼中,肝细胞的顶端区域预示着肝内胆管网络的位置。肝细胞极化的细化与内皮细胞侵入肝脏同时发生,并且这些内皮细胞沿着成熟的肝细胞基底表面迁移。通过遗传学、药理学和移植实验,我们提供证据表明内皮细胞影响相邻肝细胞的极化。内皮细胞对肝细胞的这种影响至少部分是由细胞表面蛋白玻璃心介导的,并且有助于建立协调排列的肝细胞顶端膜和均匀间隔的肝内管道。