Abstract:
Basement membranes (BMs) are sheet-like structures of extracellular matrix (ECM) that provide structural support for many tissues and play a central role in signaling. They are key regulators of cell behavior and tissue functions, and defects in their assembly or composition are involved in numerous human diseases. Due to the differences between human and animal embryogenesis, ethical concerns, legal constraints, the scarcity of human tissue material, and the inaccessibility of the in vivo condition, BM regulation during human embryo development has remained elusive. Using the post-implantation amniotic sac embryoid (PASE), we delineate BM assembly upon post-implantation development and BM disassembly during primitive streak (PS) cell dissemination. Further, we show that the transcription factor Oct4 regulates the expression of BM structural components and receptors and controls BM development by regulating Akt signaling and the small GTPase Rac1. These results represent a relevant step toward a more comprehensive understanding of early human development.
摘要:
基底膜(BM)是细胞外基质(ECM)的片状结构,为许多组织提供结构支持,并在信号传导中起核心作用。它们是细胞行为和组织功能的关键调节剂,以及它们的组装或组成中的缺陷涉及许多人类疾病。由于人类和动物胚胎发育的差异,伦理问题,法律约束,人体组织材料的稀缺,以及体内状况的难以接近,人类胚胎发育过程中的BM调节仍然难以捉摸。使用植入后羊膜囊胚状体(PASE),我们描述了植入后发育时的BM组装和原始条纹(PS)细胞传播过程中的BM分解。Further,我们发现转录因子Oct4通过调节Akt信号和小GTPaseRac1调节BM结构成分和受体的表达并控制BM发育。这些结果代表了朝着更全面地了解人类早期发展迈出的重要一步。