胃肠道(GI),用最简单的术语来说,可以描述为沿着头尾轴从口腔延伸到肛门的上皮衬里肌肉管。尽管胃肠道器官的总体结构从头到尾都是保守的,每个器官中存在不同的上皮组织结构和独特的上皮细胞类型,使每个器官都能够执行有效营养同化所需的独特消化功能。信号通路和下游转录因子的时空调控在发育过程中控制GI上皮形态发生,以赋予必要的区域特异性上皮结构和功能。这里,我们讨论了每个胃肠道器官的基本功能,并总结了沿胃肠道头尾轴存在的上皮结构的多样性。接下来,我们讨论发现,主要来自遗传小鼠模型,定义了关键转录因子在上皮形态发生过程中的作用,包括P63、SOX2、SOX15、GATA4、GATA6、HNF4A、和HNF4G。此外,我们研究刺猬,WNT,和BMP信号通路有助于沿着胃肠道的头尾轴定义独特的上皮特征。最后,我们研究了控制胃肠道内器官特异性上皮细胞类型的区域化细胞分化的分子机制,集中在胃和小肠上。小鼠中GI上皮图案化机制的描绘已经提供了指导三维GI器官型培养模型(诸如源自人多能干细胞的定向分化的那些和直接源自人组织样品的那些)的开发和改进的基本知识。对这些途径的持续检查无疑将提供对GI发育和疾病机制的重要见解,并可能为治疗GI疾病的创新组织工程和个性化医学方法提供新的途径。
The gastrointestinal (GI) tract, in simplest terms, can be described as an epithelial-lined muscular tube extending along the cephalocaudal axis from the oral cavity to the anus. Although the general architecture of the GI tract organs is conserved from end to end, the presence of different epithelial tissue structures and unique epithelial cell types within each organ enables each to perform the distinct digestive functions required for efficient nutrient assimilation. Spatiotemporal regulation of signaling pathways and downstream transcription factors controls GI epithelial morphogenesis during development to confer essential regional-specific epithelial structures and functions. Here, we discuss the fundamental functions of each GI tract organ and summarize the diversity of epithelial structures present along the cephalocaudal axis of the GI tract. Next, we discuss findings, primarily from genetic mouse models, that have defined the roles of key transcription factors during epithelial morphogenesis, including p63, SOX2, SOX15, GATA4, GATA6, HNF4A, and HNF4G. Additionally, we examine how the Hedgehog, WNT, and BMP signaling pathways contribute to defining unique epithelial features along the cephalocaudal axis of the GI tract. Lastly, we examine the molecular mechanisms controlling regionalized
cytodifferentiation of organ-specific epithelial cell types within the GI tract, concentrating on the stomach and small intestine. The delineation of GI epithelial patterning mechanisms in mice has provided fundamental knowledge to guide the development and refinement of three-dimensional GI organotypic culture models such as those derived from directed differentiation of human pluripotent stem cells and those derived directly from human tissue samples. Continued examination of these pathways will undoubtedly provide vital insights into the mechanisms of GI development and disease and may afford new avenues for innovative tissue engineering and personalized medicine approaches to treating GI diseases.