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Updated: Jun 1, 2026

A Method for Labeling Vasculature in Embryonic Mice
Published on: October 7, 2011
Cdc42 controls vascular network assembly through protein kinase Cι during embryonic vasculogenesis
Yanmei Qi1, Jie Liu, Xunwei Wu
1Department of Surgery, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, 08903-0019, USA.
Objective:
The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms.
Methods And Results:
By using genetically modified mouse embryonic stem (ES) cells, we demonstrate that ablation of the Rho GTPase Cdc42 blocks vascular network assembly during embryoid body (EB) vasculogenesis without affecting endothelial lineage differentiation. Reexpression of Cdc42 in mutant EBs rescues the mutant phenotype, establishing an essential role for Cdc42 in vasculogenesis. Chimeric analysis revealed that the vascular phenotype is caused by inactivation of Cdc42 in endothelial cells rather than surrounding cells. Endothelial cells isolated from Cdc42-null EBs are defective in directional migration and network assembly. In addition, activation of atypical protein kinase Cι (PKCι) is abolished in Cdc42-null endothelial cells, and PKCι ablation phenocopies the vascular abnormalities of the Cdc42-null EBs. Moreover, the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 depends on Cdc42 and PKCι, and expression of kinase-dead GSK-3β in Cdc42-null EBs promotes the formation of linear endothelial segments without branches. These results suggest that PKCι and GSK-3β are downstream effectors of Cdc42 during vascular morphogenesis.
Conclusions:
Cdc42 controls vascular network assembly but not endothelial lineage differentiation by activating PKCι during embryonic vasculogenesis.
Insights
The Rho GTPase Cdc42 is essential for embryonic vascular network assembly. It controls endothelial cell migration and network formation by activating PKCι and GSK-3β during vasculogenesis.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Vasculogenesis, the formation of new blood vessels, is crucial for embryonic development.
- The Rho GTPase Cdc42 plays a role in various cellular processes, including cell migration and morphogenesis.
Purpose of the Study:
- To investigate the role of Cdc42 in embryonic vasculogenesis.
- To elucidate the underlying molecular mechanisms by which Cdc42 influences vascular development.
Main Methods:
- Utilized genetically modified mouse embryonic stem cells to study Cdc42 function.
- Performed embryoid body (EB) formation and vasculogenesis assays.
- Conducted chimeric analysis and isolated endothelial cells for functional studies.
- Investigated the roles of atypical protein kinase Cι (PKCι) and glycogen synthase kinase-3β (GSK-3β) as downstream effectors.
Main Results:
- Ablation of Cdc42 in mouse embryonic stem cells blocked vascular network assembly in embryoid bodies without affecting endothelial lineage differentiation.
- Cdc42 deficiency impaired endothelial cell directional migration and network formation.
- Activation of PKCι was abolished in Cdc42-null endothelial cells, and PKCι ablation mimicked the vascular defects.
- Inhibitory phosphorylation of GSK-3β at Ser9 was dependent on Cdc42 and PKCι.
Conclusions:
- Cdc42 is essential for embryonic vascular network assembly, not endothelial differentiation.
- Cdc42 controls vascular morphogenesis by activating downstream effectors PKCι and GSK-3β.
- These findings highlight a novel pathway regulating blood vessel formation during embryonic development.
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