beta8 integrins are required for vascular morphogenesis in mouse embryos.

beta8 integrins are required for vascular morphogenesis in mouse embryos.
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DOI:
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发表时间:
2002-06
期刊:
影响因子:
4.6
通讯作者:
Jiangwen Zhu;K. Motejlek;Denan Wang;K. Zang;A. Schmidt;L. Reichardt
Jiangwen Zhu;K. Motejlek;Denan Wang;K. Zang;A. Schmidt;L. Reichardt
中科院分区:
生物学2区
文献类型:
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作者:
Jiangwen Zhu;K. Motejlek;Denan Wang;K. Zang;A. Schmidt;L. Reichardt

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为了评估含有β 8亚基的整联蛋白的体内功能,我们产生了整联蛋白β 8缺陷小鼠。β 8的消融导致胚胎或围产期死亡,血管发育严重缺陷。65%的整合素β 8缺陷胚胎在妊娠中期死亡,胎盘和卵黄囊血管化不足。剩下的35%在出生后不久死于广泛的脑内出血。对整联蛋白β 8缺陷胚胎的脑组织进行检查,发现异常的血管形态发生导致毛细血管扩张和渗漏,以及异常的脑毛细血管模式。此外,在这些突变的大脑中发现了内皮细胞增生。表达研究表明,整合素β 8转录本定位于卵黄囊内皮周围的内胚层细胞和脑神经上皮的脑室周围细胞中。我们认为整合素β 8通过为卵黄囊和胚胎脑中的毛细血管生长提供适当的线索,是血管形态发生所必需的。因此,这项研究确定了一种对胚胎卵黄囊和大脑中血管形成至关重要的分子。
In order to assess the in vivo function of integrins containing the beta8 subunit, we have generated integrin beta8-deficient mice. Ablation of beta8 results in embryonic or perinatal lethality with profound defects in vascular development. Sixty-five percent of integrin beta8-deficient embryos die at midgestation, with evidence of insufficient vascularization of the placenta and yolk sac. The remaining 35% die shortly after birth with extensive intracerebral hemorrhage. Examination of brain tissue from integrin beta8-deficient embryos reveals abnormal vascular morphogenesis resulting in distended and leaky capillary vessels, as well as aberrant brain capillary patterning. In addition, endothelial cell hyperplasia is found in these mutant brains. Expression studies show that integrin beta8 transcripts are localized in endodermal cells surrounding endothelium in the yolk sac and in periventricular cells of the neuroepithelium in the brain. We propose that integrin beta8 is required for vascular morphogenesis by providing proper cues for capillary growth in both yolk sac and embryonic brain. This study thus identifies a molecule crucial for vascular patterning in embryonic yolk sac and brain.