BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier

Runa Araya, Moeko Kudo, Masako Kawano, Katsuyoshi Ishii, Tsutomu Hashikawa, Takuji Iwasato, Shigeyoshi Itohara, Tetsuya Terasaki, Atsuhiko Oohira, Yuji Mishina, Masahisa Yamada

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)417-430
Number of pages14
JournalMolecular and Cellular Neuroscience
Volume38
Issue number3
DOIs
Publication statusPublished - 2008 Jul

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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