TY - JOUR
T1 - BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier
AU - Araya, Runa
AU - Kudo, Moeko
AU - Kawano, Masako
AU - Ishii, Katsuyoshi
AU - Hashikawa, Tsutomu
AU - Iwasato, Takuji
AU - Itohara, Shigeyoshi
AU - Terasaki, Tetsuya
AU - Oohira, Atsuhiko
AU - Mishina, Yuji
AU - Yamada, Masahisa
N1 - Funding Information:
We thank Drs. J. Harry, M. Ray, H. Hama, M. Yuhki, and M. Ogawa, for their kind advice. We thank N. Kitamura, H. Kishida, and Y. Sakamaki (RIKEN BSI-RRC) for their expert technical assistance. The CAG-CAT-LacZ reporter mice were provided by Dr. J. Miyazaki. This work was supported by MEXT Grant-in-Aid for Young Scientists (B) and #16047231 to M.Y. and by the Intramural Research Program of the NIEHS, NIH (ES071003-10) to Y. M.
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mcn.2008.04.003
DO - 10.1016/j.mcn.2008.04.003
M3 - Article
C2 - 18501628
AN - SCOPUS:45649084539
VL - 38
SP - 417
EP - 430
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 3
ER -