Zorn Aaron M, Wells James M
Division of Developmental Biology, Cincinnati Children's Hospital Research, Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Int Rev Cytol. 2007;259:49-111. doi: 10.1016/S0074-7696(06)59002-3.
The embryonic endoderm gives rise to the epithelial lining of the digestive and respiratory systems and organs such as the thyroid, lungs, liver, gallbladder, and pancreas. Studies in Xenopus, zebrafish, and mice have revealed a conserved molecular pathway controlling vertebrate endoderm development. The TGFbeta/Nodal signaling pathway is at the top of this molecular hierarchy and controls the expression of a number of key transcription factors including Mix-like homeodomain proteins, Gata zinc finger factors, Sox HMG domain proteins, and Fox forkhead factors. Here we review the function of these molecules comparing and contrasting their roles in each model organism. Finally, we will describe how our understanding of the molecular pathway governing endoderm development in embryos is being used to differentiate embryonic stem cells in vitro along endodermal lineages, with the ultimate goal of making therapeutically useful tissue.
胚胎内胚层产生消化系统和呼吸系统的上皮内衬以及甲状腺、肺、肝脏、胆囊和胰腺等器官。对非洲爪蟾、斑马鱼和小鼠的研究揭示了一条控制脊椎动物内胚层发育的保守分子途径。TGFβ/结节信号通路处于这一分子层级的顶端,控制着许多关键转录因子的表达,包括Mix样同源域蛋白、Gata锌指因子、Sox HMG域蛋白和Fox叉头因子。在此,我们综述这些分子的功能,比较和对比它们在每种模式生物中的作用。最后,我们将描述我们对胚胎内胚层发育分子途径的理解是如何被用于在体外沿着内胚层谱系分化胚胎干细胞的,其最终目标是制造出具有治疗用途的组织。