Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation.Apcdd1-deficient mice exhibit a transient increase in vessel density at ages P10–P12 due to delayed vessel pruning. Moreover,Apcdd1mutant endothelial cells precociously form the paracellular component of the barrier. Conversely, mice that overexpress Apcdd1 in retina endothelial cells have reduced vessel density but increased paracellular barrier permeability. Apcdd1 thus serves to precisely modulate Wnt/Norrin signaling activity in the retinal endothelium and coordinate the timing of both vascular pruning and barrier maturation.

中文翻译：

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Wnt抑制剂Apcdd1协调视网膜血管的血管重塑和屏障成熟。

血管生成与血管内皮细胞组织特异性的获得协调对血管功能至关重要。在视网膜中，内皮细胞由于紧密的连接和低胞吞作用而形成血-视网膜屏障。虽然规范的Norrin / Fz4 / Lrp5 / 6通路对于血管生成，血管重塑和屏障成熟至关重要，但如何协调这些不同的过程仍知之甚少。在这里，我们证明了Apcdd1是Wnt /β-catenin信号的负调控因子，在血管生成和屏障形成过程中在视网膜内皮细胞中表达。Apcdd1缺陷小鼠由于延迟的血管修剪而在P10-P12岁时表现出短暂的血管密度增加。此外，Apcdd1突变的内皮细胞会早熟地形成屏障的旁细胞成分。反过来，在视网膜内皮细胞中过表达Apcdd1的小鼠血管密度降低，但细胞旁屏障通透性增加。因此，Apcdd1用于精确调节视网膜内皮中的Wnt / Norrin信号传导活性，并协调血管修剪和屏障成熟的时间。