Lineage-specific CDK activity dynamics characterize early mammalian development

Cyclin-dependent kinases (CDKs) regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment during early mammalian development. Here, we generated a mouse model expressing a CDK translocation reporter that enabled quantification of CDK activity in live single cells. By examining pre- and post-implantation mouse embryos at different stages, we observed a progressive decrease in CDK activity in cells from the trophectoderm (TE) prior to implantation. This drop seems to correlate with the available levels of ICM-derived FGF4 as CDK activity downregulation is rescued by exogenous FGF4. Furthermore, we showed that cell fate decisions in the pre-implantation embryo are not determined by the establishment of oscillatory CDK activity or overall changes in CDK activity. Finally, we uncovered the existence of conserved regulatory mechanisms in mammals by revealing lineage-specific regulation of CDK activity in TE-like human cells.