Atypical protein kinase C is essential for embryonic vascular development in mice

The atypical PKC (aPKC) subfamily constitutes PKC zeta and PKC lambda in mice, and both aPKC isoforms have been proposed to be involved in regulating various endothelial cell (EC) functions. However, the physiological function of aPKC in ECs during embryonic development has not been well understood. To address this question, we utilized Tie2-Cre to delete PKC lambda alone (PKC lambda-SKO) or both PKC lambda and PKC zeta (DKO) in ECs, and found that all DKO mice died at around the embryonic day 11.5 (E11.5), whereas a small proportion of PKC lambda-SKO mice survived till birth. PKC lambda-SKO embryos also exhibited less phenotypic severity than DKO embryos at E10.5 and E11.5, suggesting a potential compensatory role of PKC zeta for PKC lambda in embryonic ECs. We then focused on DKO embryos and investigated the effects of aPKC deficiency on embryonic vascular development. At E9.5, deletion of both aPKC isoforms reduced the diameters of vitelline artery and vein, and decreased branching from both vitelline vessels in yolk sac. Ablation of both aPKC isoforms also disrupted embryonic angiogenesis in head and trunk at the same stage, increasing apoptosis of both ECs and non-ECs. Taken together, our results demonstrated that aPKC in ECs plays an essential role in regulating cell apoptosis, angiogenesis, and embryonic survival.

Automated summary

The study revealed that aPKC plays a crucial regulatory role in cell apoptosis, angiogenesis, and embryonic survival in ECs. PKC zeta may act as a compensatory factor for PKC lambda in embryonic ECs.