Yao Lab In the Department of Obstetrics & Gynecology

Basic Science Research

We have established innovative approaches to study in vitro and in vivo pre-implantation mouse embryo development.  We seek to identify the genetic and physical determinants that are critical and sufficient for embryo development via two research projects: 

  1. Novel Role of Pluripotency Regulators in the Early Mouse Embryo
  2. Dissecting the Genetic and Physical Determinants of Early Mouse Embryo  Development

1. Novel Role of Pluripotency Regulators in the Early Mouse Embryo

The dynamic gene network and master regulators of reprogramming in the early mouse embryo are largely unknown.  We use pluripotency regulators, such as Oct4, that have established functions in embryonic stem cells, to peer into this black box.  We developed methods for morpholino-mediated Oct4 knockdown, assessment of embryonic developmental arrest phenotype, and validation experiments to establish a novel Oct4 knockdown model.  Specifically, we discovered that Oct4 has novel and critical functions in the preimplantation embryo, prior to blastocyst development, that cannot be ascertained by conventional knockout mouse models.  Further, we combined global gene expression profiling and single-embryo gene expression analysis to identify potential Oct4-regulated genes at the 2-cell stage, and proposed novel functions for Oct4. (Foygel et al., 2008, Leong et al., 2009)

We hypothesize that other pluripotency regulators known for their critical roles in embryonic stem cells, may also have novel and essential functions prior to the blastocyst stage.  We apply this paradigm, while continuing to develop new strategies, to deconstruct the gene regulatory network in the early mouse embryo.

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Taken from Foygel et al., 2008

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2. Dissecting the Genetic and Physical Determinants of Early Mouse Embryo Development

  Mouse embryos cultured in groups are known to have better developmental potential compared to those cultured singly.  The developmental advantage conferred by group culture is thought to be due to as yet defined critical threshold concentrations of secreted factors.  It is not known how very simple physical factors, such as the number of embryos per culture drop, influence development.  We hypothesize that these physical factors may affect developmental competence by modulating gene expression in the mouse embryo.  However, conventional, macro-methods of embryo culture limit the experimental conditions that can be tested.  In collaboration with the Quake Lab, we developed a microfluidics-based embryo culture platform in which precisely-defined culture volumes can be tested. (Melin et al., 2009)

Yao lab basic science

Basic Research

Taken from Melin et al., 2009

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