Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Cell. 2014 Feb 27;156(5):1032-44. doi: 10.1016/j.cell.2014.01.023. Epub 2014 Feb 13.
Transformation of pluripotent epiblast cells into a cup-shaped epithelium as the mouse blastocyst implants is a poorly understood and yet key developmental step. Studies of morphogenesis in embryoid bodies led to the current belief that it is programmed cell death that shapes the epiblast. However, by following embryos developing in vivo and in vitro, we demonstrate that not cell death but a previously unknown morphogenetic event transforms the amorphous epiblast into a rosette of polarized cells. This transformation requires basal membrane-stimulated integrin signaling that coordinates polarization of epiblast cells and their apical constriction, a prerequisite for lumenogenesis. We show that basal membrane function can be substituted in vitro by extracellular matrix (ECM) proteins and that ES cells can be induced to form similar polarized rosettes that initiate lumenogenesis. Together, these findings lead to a completely revised model for peri-implantation morphogenesis in which ECM triggers the self-organization of the embryo's stem cells.
多能胚上皮细胞向杯状上皮的转变是囊胚着床过程中一个尚未被充分理解但又非常关键的发育步骤。对胚状体形态发生的研究使人们目前相信，正是程序性细胞死亡塑造了胚上皮。然而，通过对体内和体外发育胚胎的研究，我们证明，是一种先前未知的形态发生事件而不是细胞死亡将无定形的胚上皮转变为具有极性的细胞玫瑰花结。这种转变需要基底膜刺激的整合素信号，该信号协调胚上皮细胞的极化及其顶端收缩，这是腔发生的前提。我们表明，体外可以通过细胞外基质（ECM）蛋白替代基底膜功能，并且可以诱导胚胎干细胞形成类似的起始腔发生的极化玫瑰花结。这些发现共同导致了一个完全修订的囊胚着床后形态发生模型，其中 ECM 触发胚胎干细胞的自我组织。
