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

点击翻译按钮获取中文摘要

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.