UC Irvine

Mammals are tasked with the unique process of forming trophectodermal lineages that are essential for in utero implantation. During pre-implantation stages the fertilized egg becomes the blastocyst by dividing and subsequently segregating cells into two distinct lineages, the inner cell mass (ICM) and the trophectoderm (TE). This apparently simple developmental process is sophisticated, with transcription factors, signaling networks, cell shape and relative position within the embryo each contributing to normal development of the pre-implantation embryo. Much of our current understanding of the molecular control of blastocyst formation is based on manipulating single genes, such as transcription factors and components of signaling networks, to explore their function in the process. The focus of the experiments described in this thesis was to investigate the function of bone morphogenetic protein (BMP) signaling in development of the mouse blastocyst.

I demonstrate that BMP signaling is active beginning at the 4-cell stage of mouse development and persists until late blastocyst stage. Importantly, functional analysis using genetic and pharmacologic approaches identified a novel role for the regulation of the cell cycle by BMP signaling during mouse pre-implantation development. A second major question addressed in this dissertation is how robustness is generated in the developmental process of the pre-implantation mouse embryo. A systems biology approach was used to perform computational simulations of pre-implantation stages that uncover novel design principles employed by the early mouse embryo. These models support the hypothesis that expression noise improves the ability of the cells of the early pre-implantation mouse embryo to differentiate in an appropriate manner.