BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier
BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier
复制标题
DOI：
10.1016/j.mcn.2008.04.003
复制
发表时间：
2008-07-01
影响因子：
3.5
通讯作者：
Yamada, Masahisa
中科院分区：
文献类型：
--
作者：
Araya, Runa;Kudo, Moeko;Yamada, Masahisa
骨形态发生蛋白（BMP）信号参与神经前体细胞向星形胶质细胞的分化，但其对血管生成的贡献还没有得到很好的表征。本研究探讨了BMP信号通过BMP IA型受体（BMPRIA）在早期神经发育中的作用，使用条件性敲除小鼠模型，其中Bmpr1a在端脑神经干细胞中被选择性破坏。条件突变小鼠显示出脑血管数量的显著增加，并且血管内皮生长因子（VEGF）的水平在突变星形胶质细胞中显著上调。突变小鼠还显示出新生小鼠脑微血管周围免疫球蛋白的渗漏，表明血脑屏障形成缺陷。此外，突变小鼠的星形胶质细胞终足不能环绕皮质血管。这些结果表明，星形胶质细胞中的BMPRIA信号调节VEGF的表达，以促进适当的脑血管新生，并在血脑屏障的形成中发挥作用。(C)2008年爱思唯尔公司所有战斗保留。
Bone morphogenetic protein (BMP) signaling is involved in differentiation of neural precursor cells into astrocytes, but its contribution to angiogenesis is not well characterized. This study examines the role of BMP signaling through BMP type IA receptor (BMPRIA) in early neural development using a conditional knockout mouse model, in which Bmpr1a is selectively disrupted in telencephalic neural stem cells. The conditional mutant mice show a significant increase in the number of cerebral blood vessels and the level of vascular endothelial growth factor (VEGF) is significantly upregulated in the mutant astrocytes. The mutant mice also show leakage of immunoglobulin around cerebral microvessels in neonatal mice, suggesting a defect in formation of the blood-brain-barrier. In addition, astrocytic endfeet fail to encircle cortical blood vessels in the mutant mice. These results suggest that BMPRIA signaling in astrocytes regulates the expression of VEGF for proper cerebrovascular angiogenesis and has a role on in the formation of the blood-brain-barrier. (C) 2008 Elsevier Inc. All Fights reserved.