The atypical PKC (aPKC) subfamily constitutes PKCζ and PKCλ 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 PKCλ alone (PKCλ‐SKO) or both PKCλ and PKCζ (DKO) in ECs, and found that all DKO mice died at around the embryonic day 11.5 (E11.5), whereas a small proportion of PKCλ‐SKO mice survived till birth. PKCλ‐SKO embryos also exhibited less phenotypic severity than DKO embryos at E10.5 and E11.5, suggesting a potential compensatory role of PKCζ for PKCλ 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.

中文翻译：

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非典型蛋白激酶 C 对小鼠胚胎血管发育至关重要

非典型 PKC (aPKC) 亚家族在小鼠中构成 PKCζ 和 PKCλ，并且已提出这两种 aPKC 同种型都参与调节各种内皮细胞 (EC) 功能。然而，aPKC 在胚胎发育过程中在 ECs 中的生理功能尚未得到很好的理解。为了解决这个问题，我们使用 Tie2-Cre 删除 ECs 中单独的 PKCλ (PKCλ-SKO) 或 PKCλ 和 PKCζ (DKO)，发现所有 DKO 小鼠在胚胎第 11.5 天 (E11.5) 左右死亡，而一小部分 PKCλ-SKO 小鼠存活到出生。PKCλ-SKO 胚胎在 E10.5 和 E11.5 的表型严重程度也低于 DKO 胚胎，这表明 PKCζ 在胚胎 ECs 中对 PKCλ 具有潜在的补偿作用。然后我们专注于 DKO 胚胎并研究 aPKC 缺乏对胚胎血管发育的影响。在 E9.5，两个 aPKC 亚型的缺失降低了卵黄动脉和静脉的直径，并减少了卵黄囊中两个卵黄血管的分支。两种 aPKC 同种型的消融也在同一阶段破坏了头部和躯干的胚胎血管生成，增加了 ECs 和非 ECs 的细胞凋亡。总之，我们的研究结果表明，ECs 中的 aPKC 在调节细胞凋亡、血管生成和胚胎存活中起重要作用。