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A brain-specific an...
A brain-specific angiogenic mechanism enabled by tip cell specialization
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- Schevenels, Giel (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Cabochette, Pauline (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- America, Michelle (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Vandenborne, Arnaud (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- De Grande, Line (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Guenther, Stefan (författare)
- Max Planck Inst Heart & Lung Res, ECCPS Bioinformat & Deep Sequencing Platform, Bad Nauheim, Germany.
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- He, Liqun (författare)
- Uppsala universitet,Vaskulärbiologi
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- Dieu, Marc (författare)
- Univ Namur, Mass Spectrometry Facil MaSUN, Namur, Belgium.
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- Christou, Basile (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Vermeersch, Marjorie (författare)
- Univ Libre Bruxelles ULB, Ctr Microscopy & Mol Imaging CMMI, Gosselies, Belgium.
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- Germano, Raoul F. V. (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Perez-Morga, David (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.;Univ Libre Bruxelles ULB, Ctr Microscopy & Mol Imaging CMMI, Gosselies, Belgium.
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- Renard, Patricia (författare)
- Univ Namur, Mass Spectrometry Facil MaSUN, Namur, Belgium.
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- Martin, Maud (författare)
- Karolinska Institutet,Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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- Vanlandewijck, Michael, 1982- (författare)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, Huddinge, Sweden
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- Betsholtz, Christer (författare)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, Huddinge, Sweden
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- Vanhollebeke, Benoit (författare)
- Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium.
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Univ Libre Bruxelles ULB, ULB Neurosci Inst, Dept Mol Biol, Lab Neurovasc Signaling, Gosselies, Belgium Max Planck Inst Heart & Lung Res, ECCPS Bioinformat & Deep Sequencing Platform, Bad Nauheim, Germany. (creator_code:org_t)
- Springer Nature, 2024
- 2024
- Engelska.
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 628:8009, s. 863-871
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Vertebrate organs require locally adapted blood vessels1,2. The gain of such organotypic vessel specializations is often deemed to be molecularly unrelated to the process of organ vascularization. Here, opposing this model, we reveal a molecular mechanism for brain-specific angiogenesis that operates under the control of Wnt7a/b ligands—well-known blood–brain barrier maturation signals3,4,5. The control mechanism relies on Wnt7a/b-dependent expression of Mmp25, which we find is enriched in brain endothelial cells. CRISPR–Cas9 mutagenesis in zebrafish reveals that this poorly characterized glycosylphosphatidylinositol-anchored matrix metalloproteinase is selectively required in endothelial tip cells to enable their initial migration across the pial basement membrane lining the brain surface. Mechanistically, Mmp25 confers brain invasive competence by cleaving meningeal fibroblast-derived collagen IV α5/6 chains within a short non-collagenous region of the central helical part of the heterotrimer. After genetic interference with the pial basement membrane composition, the Wnt–β-catenin-dependent organotypic control of brain angiogenesis is lost, resulting in properly patterned, yet blood–brain-barrier-defective cerebrovasculatures. We reveal an organ-specific angiogenesis mechanism, shed light on tip cell mechanistic angiodiversity and thereby illustrate how organs, by imposing local constraints on angiogenic tip cells, can select vessels matching their distinctive physiological requirements.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Nature
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- Av författaren/redakt...
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Schevenels, Giel
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Cabochette, Paul ...
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America, Michell ...
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Vandenborne, Arn ...
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De Grande, Line
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Guenther, Stefan
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visa fler...
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He, Liqun
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Dieu, Marc
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Christou, Basile
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Vermeersch, Marj ...
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Germano, Raoul F ...
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Perez-Morga, Dav ...
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Renard, Patricia
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Martin, Maud
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Vanlandewijck, M ...
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Betsholtz, Chris ...
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Vanhollebeke, Be ...
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Uppsala universitet
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Karolinska Institutet