Lineage-specific CDK activity dynamics characterize early mammalian development
Bechara Saykali,
Andy D. Tran,
James A. Cornwell,
Matthew A. Caldwell,
Paniz Rezvan Sangsari,
Nicole Y. Morgan,
Michael J. Kruhlak,
Steven D. Cappell,
Sergio Ruiz
Affiliations
Bechara Saykali
Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Andy D. Tran
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
James A. Cornwell
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Matthew A. Caldwell
Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Paniz Rezvan Sangsari
Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
Nicole Y. Morgan
Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
Michael J. Kruhlak
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Steven D. Cappell
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Sergio Ruiz
Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding author
Summary: 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.
