Impact of the extraembryonic tissues on early embryonic development: Genetic basis of abnormal body plan

早期发育的一个重要里程碑是胚胎通过一种称为滋养细胞的特殊细胞群的作用附着（或植入）到子宫壁上。早期的胚胎不仅包括构成胚胎的细胞，还包括后来形成胎盘的细胞（称为胚胎外细胞），以及包裹在发育中的胎儿周围的膜。胎盘和膜为胎儿的发育提供有效的营养和保护，是胎儿正常生长所不可缺少的。最近对小鼠的研究表明，最近植入的胚胎的正常发育取决于胚胎细胞和胚胎外细胞的相互作用。如果非胚胎细胞不能正常分化，就可能形成异常胚胎，如雌性胚胎失去x染色体（如45X0特纳综合征）和早期受孕时携带影响胚胎外细胞产生生长因子的基因突变的情况。胚胎外细胞的功能缺陷可能是导致早期妊娠失败的原因，即胚胎已成功植入，但胚胎未能形成。控制哺乳动物发育的分子机制的显著保存使我们能够使用小鼠胚胎作为人类发育的遗传模型。该项目的目的是在实验室小鼠模型中研究调节胚胎外细胞活性的分子和细胞因素。具体来说，我们关注的是一个被称为Sox17的基因，它可能与胚胎外细胞的分化有关。我们将研究该基因突变对早期胚胎发育的影响，以验证胚胎外细胞除了营养和胎儿机械保护的其他作用外，可能在确保正常胚胎形成方面发挥重要作用的假设。

An important milestone of early development is the attachment (or implantation) of the embryo to the wall of the womb through the action of a specialized population of cells known as the trophoblasts. The early conceptus comprises not only cells that make up the embryo but also those (called extraembryonic cells) that later forms the placenta, and the membranes that wrap around the developing fetus. The placenta and the membranes are indispensable for the normal fetal growth by providing the effective nourishment and protection for the developing fetus. Recent studies in the mouse have revealed that normal development of the recently implanted conceptus depends on the reciprocal interaction of the embryonic and extraembryonic cells. Abnormal embryo may form if the non-embryonic cells do not differentiate normally, as seen in the situation when an X-chromosome is lost from the female embryo (as in 45X0 Turner syndrome) and in early conceptus that carries a gene mutation that affects the production of growth factors by the extraembryonic cells. Functional deficiency of the extraembryonic cells might be a cause for early pregnancy loss where the conceptus has successfully implanted but the embryo fails to form. The remarkable conservation of the molecular mechanism that controls mammalian development allows us to use the mouse embryo as a genetic model for human development. The proposed project is designed to examine in a laboratory mouse model the molecular and cellular factors that regulate the activity of the extraembryonic cells. Specifically, we focus on a gene known as Sox17, which may be involved with the differentiation of the extraembryonic cells. We will study the impact of the mutation of this gene on the development of the early embryo to test the hypothesis that the extraembryonic cells may fulfill an important function in ensuring normal embryo formation, in addition to the other roles of nourishment and mechanical protection of the fetus.