Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge, CB2 3EG, UK; California Institute of Technology, Division of Biology and Biological Engineering, 1200 E. California Boulevard, Pasadena, CA, 91125, USA; Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, 07070, Turkey; Yale University School of Medicine, Department of Genetics, New Haven, CT, 06510, USA.
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, 07070, Turkey.
Dev Biol. 2021 Feb;470:84-94. doi: 10.1016/j.ydbio.2020.11.005. Epub 2020 Nov 17.
At implantation, the mouse embryo undergoes a critical transformation which requires the precise spatiotemporal control of signalling pathways necessary for morphogenesis and developmental progression. The role played by such signalling pathways during this transition are largely unexplored, due to the inaccessibility of the embryo during the implantation when it becomes engulfed by uterine tissues. Genetic studies demonstrate that mutant embryos for BMPs die around gastrulation. Here we have aimed to dissect the role of BMPs during pre-to post-implantation transition by using a protocol permitting the development of the embryo beyond implantation stages in vitro and using stem cells to mimic post-implantation tissue organisation. By assessing both the canonical and non-canonical mechanisms of BMP, we show that the loss of canonical BMP activity compromises the extra-embryonic ectoderm development. Our analyses demonstrate that BMP signalling maintains stem cell populations within both embryonic/extra-embryonic tissues during pre-to post-implantation development. These results may provide insight into the role played by BMP signalling in controlling early embryogenesis.
在着床时,小鼠胚胎经历了一个关键的转变,这需要信号通路在形态发生和发育进展方面的精确时空控制。由于胚胎在着床时被子宫组织吞噬而无法接近,因此这种信号通路在这个转变过程中的作用在很大程度上尚未被探索。遗传研究表明,BMPs 的突变胚胎在原肠胚形成期左右死亡。在这里,我们旨在通过使用一种允许胚胎在体外超越着床阶段发育的方案,并使用干细胞来模拟着床后组织的组织,来剖析 BMPs 在着床前到着床后的过渡中的作用。通过评估 BMP 的经典和非经典机制,我们表明经典 BMP 活性的丧失会损害胚胎外胚层的发育。我们的分析表明,BMP 信号在着床前到着床后的发育过程中维持着胚胎/胚胎外组织内的干细胞群体。这些结果可能为 BMP 信号在控制早期胚胎发生中的作用提供了一些见解。