PT  - JOURNAL ARTICLE
AU  - Saykali, Bechara
AU  - Tran, Andy D.
AU  - Cornwell, James A.
AU  - Caldwell, Matthew A.
AU  - Sangsari, Paniz Rezvan
AU  - Morgan, Nicole Y.
AU  - Kruhlak, Michael J.
AU  - Cappell, Steven D.
AU  - Ruiz, Sergio
TI  - Lineage-specific CDK activity dynamics characterize early mammalian development
AID  - 10.1101/2024.06.14.599098
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.06.14.599098
4099  - http://biorxiv.org/content/early/2024/06/14/2024.06.14.599098.short
4100  - http://biorxiv.org/content/early/2024/06/14/2024.06.14.599098.full
AB  - Cyclin-dependent kinases (CDK) are key regulatory enzymes that regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment in vivo during early mammalian development. Here, we generated a transgenic mouse model expressing a CDK kinase translocation reporter (KTR) 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 correlated with the establishment of an FGF4-dependent signaling gradient through the embryonic-abembryonic axis. Furthermore, we showed that CDK activity levels do not determine cell fate decisions during pre-implantation development. Finally, we uncovered the existence of conserved regulatory mechanisms in mammals by revealing lineage-specific regulation of CDK activity in TE-like human cells.Competing Interest StatementThe authors have declared no competing interest.