California Institute of Technology, Division of Biology and Biological Engineering, 1200 E. California Boulevard, Pasadena, CA, 91125, USA; Yale University School of Medicine, Department of Genetics, New Haven, CT, 06510, USA.
California Institute of Technology, Division of Biology and Biological Engineering, 1200 E. California Boulevard, Pasadena, CA, 91125, USA; Developmental Dynamics Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Dev Biol. 2021 Jun;474:82-90. doi: 10.1016/j.ydbio.2020.12.005. Epub 2020 Dec 15.
Breaking embryonic symmetry is an essential prerequisite to shape the initially symmetric embryo into a highly organized body plan that serves as the blueprint of the adult organism. This critical process is driven by morphogen signaling gradients that instruct anteroposterior axis specification. Despite its fundamental importance, what triggers symmetry breaking and how the signaling gradients are established in time and space in the mammalian embryo remain largely unknown. Stem cell-based in vitro models of embryogenesis offer an unprecedented opportunity to quantitatively dissect the multiple physical and molecular processes that shape the mammalian embryo. Here we review biochemical mechanisms governing early mammalian patterning in vivo and highlight recent advances to recreate this in vitro using stem cells. We discuss how the novel insights from these model systems extend previously proposed concepts to illuminate the extent to which embryonic cells have the intrinsic capability to generate specific, reproducible patterns during embryogenesis.
打破胚胎对称性是将最初对称的胚胎塑造成高度组织化的身体蓝图的必要前提,该蓝图是成年生物体的蓝图。这个关键过程是由形态发生素信号梯度驱动的,该梯度指导前后轴的指定。尽管它非常重要,但是什么触发了对称性的破坏,以及信号梯度如何在哺乳动物胚胎中及时且适当地建立,在很大程度上仍然未知。基于干细胞的胚胎发生体外模型为定量剖析塑造哺乳动物胚胎的多个物理和分子过程提供了前所未有的机会。在这里,我们回顾了体内控制早期哺乳动物模式形成的生化机制,并强调了最近利用干细胞重现这一过程的进展。我们讨论了这些模型系统中的新见解如何扩展以前提出的概念,以阐明胚胎细胞在胚胎发生过程中具有内在能力产生特定、可重复的模式的程度。