Cell fate decisions and organization in the early mammalian embryo

We study the molecular mechanisms by which single cells acquire distinct fates during development, and communicate with each other and the environment to reproducibly form an embryo with the correct proportions and spatial patterns of different cell types. By understanding how cellular states are controlled in the embryo, we also aim to stably reproduce these states in vitro, in form of novel embryo-derived stem cell types.
We use the preimplantation mouse embryo as an in vivo model system to study these questions in a physiological setting, taking advantage of its small size, low complexity, and ease of experimental manipulation.​​

Preimplantation development in the mouse
Three cell types, the epiblast (EPI), the trophectoderm (TE) and the primitive endoderm (PE) arise from two consecutive decisions, and self-organize to construct the blastocyst. EPI cells will give rise to the fetus, while TE and PE cells will make extraembryonic tissues, such as the placenta and the yolk sac endoderm, respectively, to support fetal development following implantation. 

• Exploiting our recently developed genome editing method, termed 2C-HR-CRISPR (Gu and Posfai, 2018 Nature Biotechnology) we engineer the embryo genome and create genetically encoded tools to visualize (e.g. fluorescent protein or RNA reporters) and manipulate (e.g. protein degron systems, optogenetic constructs and other synthetic biology tools) molecular events.

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• Using light sheet microscopy, we query these processes in live embryos, allowing us to address the spatial and temporal dynamics of molecular regulation in vivo.

2C-HR-CRISPR microinjections

Live triple-color reporter blastocyst, in which all three cell lineages are differentially visualized by tagging endogenous transcription factors with different reporters (Cdx2 - trophectoderm; Nanog - epiblast; Gata6 - primitive endoderm)