BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier.
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.
Araya
Runa
R
Yamada Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Kudo
Moeko
M
Kawano
Masako
M
Ishii
Katsuyoshi
K
Hashikawa
Tsutomu
T
Iwasato
Takuji
T
Itohara
Shigeyoshi
S
Terasaki
Tetsuya
T
Oohira
Atsuhiko
A
Mishina
Yuji
Y
Yamada
Masahisa
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D042461:Vascular Endothelial Growth Factor A; D052005:Bone Morphogenetic Protein Receptors, Type I