Doctoral Researcher Max Planck Institute for Molecular Biomedicine, Nordrhein-Westfalen, Germany
Abstract: Time is a dimension where events occur in a linear sequence, governed by cause-and-effect, avoiding causality paradoxes. Living systems obey the basic laws of nature that define the cause-and-effect sequence of events. Fundamental processes such as cell fate specification, differentiation and morphogenesis occur in a precise order to avoid conflicts. This indicates the existence of molecular factors that temporally coordinate these events. If their function is disrupted, developmental events could be initiated prematurely. The identification of such factors, their roles and effects of their disruption are of fundamental biological importance. Using the mouse embryo model system, we studied the temporal control of tissue morphogenesis during blastocyst formation. Defects in cell lineage segregation and tissue scale organisation during this process can severely impair further embryonic development. Yet, the molecular control that coordinates tissue morphogenesis and cell fate dynamics in the developing blastocyst is poorly understood. A major driver of embryonic morphogenesis is the establishment of epithelial polarity which forms tissue barriers and luminal spaces at defined developmental time points. While the extraembryonic tissues establish epithelial polarity during the preimplantation stages, the epiblast cells undergo epithelialisation only after implantation, upon exiting naive pluripotency. The developmental significance and factors that control this temporal sequence remain elusive. To decipher this process we focussed on the transcriptional regulation and tissue morphogenesis of the pluripotent lineage. Analysis of genome occupancy dynamics and loss of function effects at sequential stages of the early embryogenesis revealed that the developmental timing of epiblast polarisation is controlled by the cooperative activity of the core pluripotency transcription factors Oct4 and Sox2. Our results indicate that the pluripotent cells are actively sustained in an apolar state, allowing timely segregation of the epiblast and the primitive endoderm, hence laying the foundation to build on the further development of the embryo. Thus, our study has revealed a novel, physiological role of Oct4 and Sox2 in tissue morphogenesis and cell fate dynamics in the early mouse embryo.
