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Fgfbp1 promotes blo...
Fgfbp1 promotes blood-brain barrier development by regulating collagen IV deposition and maintaining Wnt/beta-catenin signaling
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- Cottarelli, Azzurra (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.;Columbia Univ, Dept Neurol, Irving Med Ctr, New York, NY 10032 USA.
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- Corada, Monica (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.
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- Beznoussenko, Galina, V (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.
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- Mironov, Alexander A. (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.
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- Globisch, Maria A. (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Biswas, Saptarshi (author)
- Columbia Univ, Dept Neurol, Irving Med Ctr, New York, NY 10032 USA.
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- Huang, Hua, 1986- (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Dimberg, Anna (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Magnusson, Peetra (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Agalliu, Dritan (author)
- Columbia Univ, Dept Neurol, Irving Med Ctr, New York, NY 10032 USA.;Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, New York, NY 10032 USA.
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- Lampugnani, Maria Grazia (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.;Ist Ric Farmacolog Mario Negri, I-20156 Milan, Italy.
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- Dejana, Elisabetta (author)
- FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy.;Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, S-75237 Uppsala, Sweden.;Univ Milan, Sch Med, Dept Oncol & Haematooncol, I-20122 Milan, Italy.
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FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy;Columbia Univ, Dept Neurol, Irving Med Ctr, New York, NY 10032 USA. FIRC Inst Mol Oncol Fdn IFOM, I-20139 Milan, Italy. (creator_code:org_t)
- 2020-01-01
- 2020
- English.
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In: Development. - : COMPANY BIOLOGISTS LTD. - 0950-1991 .- 1477-9129. ; 147:16
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https://doi.org/10.1...
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Abstract
Subject headings
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- Central nervous system (CNS) blood vessels contain a functional blood-brain barrier (BBB) that is necessary for neuronal survival and activity. Although Wnt/beta-catenin signaling is essential for BBB development, its downstream targets within the neurovasculature remain poorly understood. To identify targets of Wnt/beta-catenin signaling underlying BBB maturation, we performed a microarray analysis that identified Fgfbp1 as a novel Wnt/beta-catenin-regulated gene in mouse brain endothelial cells (mBECs). Fgfbp1 is expressed in the CNS endothelium and secreted into the vascular basement membrane during BBB formation. Endothelial genetic ablation of Fgfbp1 results in transient hypervascularization but delays BBB maturation in specific CNSregions, as evidenced by both upregulation of Plvap and increased tracer leakage across the neurovasculature due to reduced Wnt/beta-catenin activity. In addition, collagen IV deposition in the vascular basement membrane is reduced in mutant mice, leading to defective endothelial cell-pericyte interactions. Fgfbp1 is required cell-autonomously in mBECs to concentrate Wnt ligands near cell junctions and promote maturation of their barrier properties in vitro. Thus, Fgfbp1 is a crucial extracellular matrix protein during BBB maturation that regulates cell-cell interactions and Wnt/beta-catenin activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Blood-brain barrier
- Fgfbp1
- Wnt/beta-catenin signaling
- Basement membrane
- Collagen IV
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cottarelli, Azzu ...
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Corada, Monica
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Beznoussenko, Ga ...
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Mironov, Alexand ...
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Globisch, Maria ...
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Biswas, Saptarsh ...
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Huang, Hua, 1986 ...
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Dimberg, Anna
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Magnusson, Peetr ...
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Agalliu, Dritan
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Lampugnani, Mari ...
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Dejana, Elisabet ...
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