Department of Cell Biology, University of Miami School of Medicine, Miami, Florida, USA.
Mol Cell Biol. 2014 Feb;34(3):560-72. doi: 10.1128/MCB.00937-13. Epub 2013 Nov 25.
We analyzed the mechanism of developmental failure in implanted β1 integrin-null blastocysts and found that primitive endoderm cells are present but segregate away from, instead of forming an epithelial layer covering, the inner cell mass. This cell segregation phenotype was also reproduced in β1 integrin-null embryoid bodies, in which primitive endoderm cells segregated and appeared as miniature aggregates detached from the core spheroids, and a primitive endoderm layer failed to form on the surface. Restricted β1 integrin gene deletion in embryos using Ttr-Cre or Sox2-Cre indicated that the loss of integrin function in the cells of the inner core rather than the outer layer is responsible for the failure to form a primitive endoderm layer. We conclude that β1 integrin is essential for the attachment of the primitive endoderm layer to the epiblast during the formation of a basement membrane, a process concurrent with the transition from cadherin- to integrin-mediated cell adhesion.
我们分析了植入的β1 整合素缺失的囊胚发育失败的机制，发现原始内胚层细胞存在，但它们分离出来，而不是形成覆盖内细胞团的上皮层。这种细胞分离表型也在β1 整合素缺失的类胚体中重现，其中原始内胚层细胞分离，形成与核心球体分离的微小聚集物，并且表面未能形成原始内胚层层。使用 Ttr-Cre 或 Sox2-Cre 在胚胎中限制β1 整合素基因的缺失表明，整合素功能的丧失是在内核细胞中而不是在外层细胞中，这导致了原始内胚层层无法形成。我们得出结论，β1 整合素对于在形成基底膜的过程中原始内胚层层附着到上胚层是必不可少的，这是一个与从钙粘蛋白介导的细胞粘附到整合素介导的细胞粘附的转变同时发生的过程。
