Vascular development of the brain requires β8 integrin expression in the neuroepithelium
Vascular development of the brain requires β8 integrin expression in the neuroepithelium
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DOI：
10.1523/jneurosci.3467-05.2005
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发表时间：
2005-10-26
影响因子：
5.3
通讯作者：
Reichardt, LF
中科院分区：
文献类型：
--
作者：
Proctor, JM;Zang, KL;Reichardt, LF
我们之前表明，形成αvβ8异二聚体的整合素β8亚基的缺失会导致卵黄囊、胎盘和大脑中的血管发育异常。缺乏整合素β8（itgβ8）基因的动物要么在妊娠中期因胎盘和卵黄囊血管化不足而死亡，要么在出生后不久因严重脑出血而死亡。为了特别关注大脑中含有 β 8 亚基的整合素的作用，并避免早期致死，我们使用了一种靶向删除策略，仅从大脑内的细胞类型中删除 itg β 8。从血管内皮细胞或迁移神经元中消除 itg beta 8 不会导致脑出血。然而，从神经上皮中定向删除 itg beta 8 会导致出生后第 0 天出现双侧出血，尽管该表型不如 itg beta 8 缺失的动物严重。神经上皮细胞缺乏 itg beta 8 的新生小鼠会出现皮质、神经节隆起和丘脑出血，以及血管形态发生异常和神经胶质细胞紊乱。有趣的是，缺乏来自神经上皮细胞的 itg beta 8 的成年小鼠没有表现出出血迹象。我们认为，血管内皮细胞和缺乏 itg beta 8 的神经胶质细胞之间的缺陷关联是造成发育过程中出现的脉管系统渗漏的原因，但一种未识别的补偿机制在出生后修复了脉管系统。
We showed previously that loss of the integrin beta 8 subunit, which forms alpha v beta 8 heterodimers, results in abnormal vascular development in the yolk sac, placenta, and brain. Animals lacking the integrin beta 8 (itg beta 8) gene die either at midgestation, because of insufficient vascularization of the placenta and yolk sac, or shortly after birth with severe intracerebral hemorrhage. To specifically focus on the role of integrins containing the beta 8 subunit in the brain, and to avoid early lethalities, we used a targeted deletion strategy to delete itg beta 8 only from cell types within the brain. Ablating itg beta 8 from vascular endothelial cells or from migrating neurons did not result in cerebral hemorrhage. Targeted deletion of itg beta 8 from the neuroepithelium, however, resulted in bilateral hemorrhage at postnatal day 0, although the phenotype was less severe than in itg beta 8-null animals. Newborn mice lacking itg beta 8 from the neuroepithelium had hemorrhages in the cortex, ganglionic eminence, and thalamus, as well as abnormal vascular morphogenesis, and disorganized glia. Interestingly, adult mice lacking itg beta 8 from cells derived from the neuroepithelium did not show signs of hemorrhage. We propose that defective association between vascular endothelial cells and glia lacking itg beta 8 is responsible for the leaky vasculature seen during development but that an unidentified compensatory mechanism repairs the vasculature after birth.