Preimplantation development encompasses the period from fertilization to implantation. These early embryos are the source of Embryonic stem (ES) cells and the locus of nuclear reprogramming. Therefore, the molecular study of these early embryos is very important for stem cell biology and its potential therapeutic applications to aging and dysfunctional organs/tissues. Our goal is to apply systematic genomic approaches to these early embryos and to understand their regulation of gene expression. We carried out DNA microarray-based global expression profiling of all preimplantation stages in mouse, which revealed and characterized the distinctive patterns of maternal RNA degradation and two major transient waves of de novo transcription: zygotic genome activation (ZGA) and mid-preimplantation gene activation (MGA). Through these analyses, we identified a number of genes that show unique expression patterns. We have demonstrated that one of them, named Zga1, is expressed exclusively in 2-cell mouse embryos and ES cells and plays a critical role in the progression of preimplantation development. We also found that a gene called Chuk shows constant RNA levels throughout preimplantation development and can be used as an internal standard suitable for quantitative RT-PCR (Falco et al., 2006). We also developed a technique to do large-scale Whole Mount In Situ Hybridization (WISH), which allows us to reveal the spatial expression patterns of 91 genes in mouse preimplantation embryos (Yoshikawa et al., 2006). We are currently studying the functions of these genes in details.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000655-08
Application #
7325191
Study Section
(LG)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Vallejo, Griselda; Maschi, DarĂ­o; Mestre-Citrinovitz, Ana C et al. (2010) Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells. J Cell Physiol 222:127-37
Vallee, Maud; Aiba, Kazuhiro; Piao, Yulan et al. (2008) Comparative analysis of oocyte transcript profiles reveals a high degree of conservation among species. Reproduction 135:439-48
Falco, Geppino; Lee, Sung-Lim; Stanghellini, Ilaria et al. (2007) Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells. Dev Biol 307:539-50
Hamatani, Toshio; Ko, Minoru Sh; Yamada, Mitsutoshi et al. (2006) Global gene expression profiling of preimplantation embryos. Hum Cell 19:98-117
Rogers, N T; Halet, G; Piao, Y et al. (2006) The absence of a Ca(2+) signal during mouse egg activation can affect parthenogenetic preimplantation development, gene expression patterns, and blastocyst quality. Reproduction 132:45-57
Falco, Geppino; Stanghellini, Ilaria; Ko, Minoru S H (2006) Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos. Reprod Biomed Online 13:394-403
Park, Jung-Min; Kohn, Matthew J; Bruinsma, Monique W et al. (2006) The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells. Mol Cell Biol 26:1445-51
Yoshikawa, Toshiyuki; Piao, Yulan; Zhong, Jinhui et al. (2006) High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization. Gene Expr Patterns 6:213-24
Ko, Minoru S H (2006) Expression profiling of the mouse early embryo: reflections and perspectives. Dev Dyn 235:2437-48
Ko, Minoru S H (2005) Molecular biology of preimplantation embryos: primer for philosophical discussions. Reprod Biomed Online 10 Suppl 1:80-7

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