关键词: Blastulation Embryonic biomechanics Gastrulation Implantation Mechanosignaling Mechanotransduction Stem cell embryo models

Mesh : Animals Humans Embryonic Development Embryo, Mammalian / cytology embryology metabolism Biomechanical Phenomena

来  源:   DOI:10.1016/bs.ctdb.2024.05.001

Abstract:
Biomechanics in embryogenesis is a dynamic field intertwining the physical forces and biological processes that shape the first days of a mammalian embryo. From the first cell fate bifurcation during blastulation to the complex symmetry breaking and tissue remodeling in gastrulation, mechanical cues appear critical in cell fate decisions and tissue patterning. Recent strides in mouse and human embryo culture, stem cell modeling of mammalian embryos, and biomaterial design have shed light on the role of cellular forces, cell polarization, and the extracellular matrix in influencing cell differentiation and morphogenesis. This chapter highlights the essential functions of biophysical mechanisms in blastocyst formation, embryo implantation, and early gastrulation where the interplay between the cytoskeleton and extracellular matrix stiffness orchestrates the intricacies of embryogenesis and placenta specification. The advancement of in vitro models like blastoids, gastruloids, and other types of embryoids, has begun to faithfully recapitulate human development stages, offering new avenues for exploring the biophysical underpinnings of early development. The integration of synthetic biology and advanced biomaterials is enhancing the precision with which we can mimic and study these processes. Looking ahead, we emphasize the potential of CRISPR-mediated genomic perturbations coupled with live imaging to uncover new mechanosensitive pathways and the application of engineered biomaterials to fine-tune the mechanical conditions conducive to embryonic development. This synthesis not only bridges the gap between experimental models and in vivo conditions to advancing fundamental developmental biology of mammalian embryogenesis, but also sets the stage for leveraging biomechanical insights to inform regenerative medicine.
摘要:
胚胎发生中的生物力学是一个动态场,它将塑造哺乳动物胚胎的第一天的物理力和生物过程交织在一起。从囊胚化过程中的第一次细胞命运分叉到原肠胚化过程中复杂的对称性破坏和组织重塑,机械提示在细胞命运决定和组织模式中显得至关重要。小鼠和人类胚胎培养的最新进展,哺乳动物胚胎的干细胞建模,生物材料的设计揭示了细胞力的作用,细胞极化,以及影响细胞分化和形态发生的细胞外基质。本章强调了胚泡形成中生物物理机制的基本功能,胚胎植入,和早期原肠胚形成,细胞骨架和细胞外基质刚度之间的相互作用协调了胚胎发生和胎盘规范的复杂性。像胚状体这样的体外模型的发展,gastruloids,和其他类型的胚状体,已经开始忠实地概括人类的发展阶段,为探索早期发展的生物物理基础提供了新的途径。合成生物学和先进生物材料的整合正在提高我们模拟和研究这些过程的精度。展望未来,我们强调CRISPR介导的基因组扰动与实时成像相结合的潜力,以发现新的机械敏感途径,并应用工程生物材料来微调有利于胚胎发育的机械条件.这种合成不仅弥合了实验模型和体内条件之间的差距,以推进哺乳动物胚胎发生的基本发育生物学,但也为利用生物力学见解为再生医学提供信息奠定了基础。
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