Academic Journal
A brain-specific angiogenic mechanism enabled by tip cell specialization.
| العنوان: | A brain-specific angiogenic mechanism enabled by tip cell specialization. |
|---|---|
| المؤلفون: | Schevenels, Giel, Cabochette, Pauline, America, Michelle, Vandenborne, Arnaud, De Grande, Line, Guenther, Stefan, He, Liqun, Dieu, Marc, Christou, Basile, Vermeersch, Marjorie, Germano, Raoul F V, Perez-Morga, David, Renard, Patricia, Martin, Maud, Vanlandewijck, Michael, Betsholtz, Christer, Vanhollebeke, Benoît |
| المصدر: | Nature (London), 628 (8009 |
| سنة النشر: | 2024 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Sciences bio-médicales et agricoles, Animals, Basement Membrane -- metabolism, Blood-Brain Barrier -- metabolism -- cytology, Brain -- cytology -- blood supply -- metabolism, Cell Movement, Collagen Type IV -- metabolism, CRISPR-Cas Systems -- genetics, Endothelial Cells -- metabolism -- cytology, Meninges -- cytology -- blood supply -- metabolism, Neovascularization, Physiologic, Organ Specificity, Wnt Proteins -- metabolism, Wnt Signaling Pathway, Zebrafish -- genetics -- metabolism, Zebrafish Proteins -- metabolism -- genetics |
| الوصف: | 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 signals3-5. 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. ; SCOPUS: ar.j ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| Relation: | uri/info:pmid/38570687; uri/info:scp/85189206369; uri/info:pmcid/PMC11041701; https://dipot.ulb.ac.be/dspace/bitstream/2013/378099/1/doi_361743.pdf |
| الاتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/378099 https://dipot.ulb.ac.be/dspace/bitstream/2013/378099/1/doi_361743.pdf |
| رقم الانضمام: | edsbas.C2B78F86 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |