National Institute on Aging
National Institutes of Health
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Intramural
Developmental Genomics and Aging Section
Minoru S.H. Ko, M.D., Ph.D., Chief
Senior Investigator
2. Preimplantation Mouse Development
Preimplantation development is an important model system to study the pluripotency of mouse cells. Concerning the differentiation potential of cells, preimplantation development can be seen as a process in which totipotent stem cells (fertilized eggs) lose their totipotency. Preimplantation development also has many other interesting features as a biological system. First, it involves dynamic switching from a process governed by the activity of maternally stored RNA/proteins to a process governed by the genes of zygotic activation. Some oocyte mRNAs are translated, but fertilization triggers massive mRNA degradation. Transcription from the zygotic genome begins at the late one-cell to two-cell stage in mouse. Although it is well established that this transition is regulated by a "zygotic clock", it is not known what type(s) of genes is activated first or how genes are activated. Second, the first cell differentiation event in the mammalian development occurs in preimplantation embryos. The process, "compaction", occurs at the 8- to 16-cell stage, when cells that were previously loosely associated begin to adhere in the tightly organized cell mass of the morula. This is the starting point for cell differentiation into Inner Cell Mass (ICM) (which eventually becomes the embryo) and Trophectoderm (which eventually becomes the placenta). Despite its importance, the molecular study of preimplantation development has been significantly delayed, mainly because of the scarcity of the materials for molecular biological/biochemical approaches.
In our previous work, we identified many genes that show stage-specific expression patterns during preimplantation mouse development. However, these genes have been identified by EST frequency, which is a relatively inaccurate and far from ideal way to do gene expression profiling. The cDNA microarray-based gene expression profiling will provide more reliable information. To this end, we have been working on a large-scale gene expression profiling of each stage of preimplantation mouse development using the NIA mouse 15K cDNA microarrays.
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Updated: Thursday October 11, 2007