From blastocyst to egg cylinder: analysis of peri-implantation embryogenesis

从囊胚到卵筒：植入前胚胎发生分析

• 批准号: 278835329
• 负责人: Dr. Ivan Bedzhov
• 金额: --
• 依托单位: Forschungsgruppe Embryonic Self-Organization
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/278835329?language=en
• 关键词: blastocyst; egg; cylinder; analysis; peri

Four and a half days after fertilization the mouse embryo comes for the first time in direct contact with the maternal environment and initiates implantation. In turn, the maternal tissues proliferate and engulf the embryo making it relatively inaccessible for direct observations and experimental manipulations. Thus, the peri- implantation embryogenesis is largely unexplored and probably the most enigmatic period of mouse development. Just within 24 hours the implanting blastocyst dramatically changes its shape transforming into an elongated egg cylinder. At that time the pluripotent epiblast undergoes global reorganization from a simple ball of cells into a cup- shaped polarized epithelium surrounding a central proamniotic cavity. The emergence of this new organization of the embryonic lineage provides a platform for establishment of the germ layers building the embryo proper. Apoptosis was originally considered as the driving force for reshaping the epiblast during the peri-implantation stages. Contrary to this view we found a previously unknown, apoptosis- independent morphogenic event that reorganizes the epiblast into radially polarized rosette-like structure, serving as a foundation for proper establishment of the egg cylinder. Taking advantage of novel methods for embryo and embryonic stem-cell cultures we will dissect the processes of epiblast polarization and lumenogenesis on cellular and molecular levels. To elucidate the developmental regulation of epiblast morphogenesis we will investigate signalling circuits involved in pluripotent state transitions in relation to acquisition of epithelial polarity.

受精4天半后，小鼠胚胎第一次与母体环境直接接触并开始着床。反过来，母体组织增殖并吞噬胚胎，使其相对难以直接观察和实验操作。因此，着床期胚胎发生在很大程度上是未知的，可能是小鼠发育中最神秘的时期。仅仅在24小时内，植入的囊胚就会戏剧性地改变形状，变成一个细长的卵圆柱体。此时，多能性外胚层经历全局重组，从一个简单的细胞球变成围绕着中央羊膜原腔的杯状极化上皮。这种胚胎谱系的新组织的出现为建立胚层提供了一个平台。细胞凋亡最初被认为是外胚层在着床期重塑的驱动力。与此观点相反，我们发现了一个先前未知的、不依赖于细胞凋亡的形态发生事件，该事件将外胚层重组为径向极化的玫瑰状结构，为卵筒的适当建立奠定了基础。利用胚胎和胚胎干细胞培养的新方法，我们将在细胞和分子水平上解剖外胚层极化和放光发生的过程。为了阐明外胚层形态发生的发育调控，我们将研究与上皮极性获取相关的多能状态转变的信号通路。