Health Research and Policy–

Abstract

DATE:

April 16, 2009

TIME:

1:15-3:00 pm

LOCATION:

Center for Clinical Sciences Research (CCSR), Rm 4205

TITLE:

A Portal to the Gene Regulatory Network in the Early Embryo

SPEAKER:

Mylene W.M. Yao, MD
Assistant Professor, Dept of Obstetrics and Gynecology
Stanford University School of Medicine

Contributors from Yao Lab: Kira Foygel1, Denise Leong1, Annett Hahn-Windgassen1, Zena Kharsa2, and Sunny Jun1.
Contributors from the Wong Lab: Bokyung Choi1, Wing H. Wong4.

1Department of Obstetrics and Gynecology, Stanford University School of Medicine
2Department of Biology,
3Department of Applied Physics, and
4Department of Statistics, School of Humanities and Sciences, Stanford University, CA, USA.

During the peri-implantation stages of mouse development, the early embryo is dramatically reprogrammed to establish totipotent blastomeres, followed by emergence of the first two differentiated lineages -- the trophectoderm, which forms the placenta, and the inner cell mass, which gives rise to the developing fetus and is also the source of embryo-derived embryonic stem cell (ESC) lines. These early stages hold the key to Nature’s reprogramming toolkit for perpetuating the species. However, compared to the embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that ESC pluripotency regulators that are highly expressed at the 1- to 2-cell stages in mouse embryos, may be critical regulators of the earliest gene network during the maternal-embryonic transition. By combining antisense morpholino oligonucleotide-mediated gene knockdown with gene expression analysis at the global and single-embryo levels, we have discovered that Oct4, Sall4, and other pluripotency regulators are required for development prior to the blastocyst stage. Specifically, Oct4 is required for setting the correct transcriptional and post-transcriptional program, as early as the 2-cell stage. Our data suggest that co- and cross-regulation amongst Oct4, the general transcriptional machinery, and epigenetic regulators may be a critical part of this dynamic gene network. We envision that key pluripotency regulators serve as key "portals" for deconstructing the dynamic gene network that directs development, cell fate decisions, and the establishment of the ESC gene network.

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