PXD042613

PXD042613 is an original dataset announced via ProteomeXchange.

Title	An organ-specific angiogenic control mechanism for endothelial tailoring.
Description	Each organ of the human body requires locally-adapted blood vessels1–3. The gain of such organotypic vessel specializations is often deemed molecularly unrelated to the process of organ vascularization. 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 signals4–6. The control mechanism relies on Wnt7a/b-dependent expression of Mmp25 in brain endothelial cells. This hitherto poorly characterized GPI-anchored matrix metalloproteinase is selectively required in endothelial tip cells to enable their initial migration across the pial basement membrane which lines the brain surface, and whose distinctive molecular composition is controlled by embryonic pial fibroblasts. Mechanistically, Mmp25 confers brain invasive competence by cleaving the pial basement membrane-enriched Col4a5/6 within a short non-collagenous region of the central helical part of the heterotrimer. Upon genetic interference with pial basement membrane composition, the Wnt/β-catenin-dependent organotypic control of brain angiogenesis is lost, resulting in a properly patterned, yet blood-brain barrier-defective cerebrovasculature. This work reveals an organ-specific angiogenesis mechanism, sheds light on tip cell mechanistic angiodiversity, and thereby illustrates how organs, by imposing local constraints on angiogenic tip cells, can select vessels matching their distinctive physiological requirements.
HostingRepository	PRIDE
AnnounceDate	2024-02-08
AnnouncementXML	Submission_2024-02-08_02:40:51.803.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042613
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marc Dieu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	hydroxylated proline; hydroxylated lysine; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-01 05:34:12	ID requested
⏵ 1	2024-02-08 02:40:52	announced

10.6019/PXD042613;

submitter keyword: Angiogenesis

tip cell angiodiversity

Wnt/β-catenin signaling

blood-brain barrier

BBB

Mmp25

Col4a5

Col4a6

Pial fibroblast

Gpr124

Reck

Wnt7a

Benoit Vanhollebeke
contact affiliation	Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), Gosselies B-6041, Belgium
contact email	Benoit.Vanhollebeke@ulb.be
lab head
Marc Dieu
contact affiliation	University of Namur - MaSUN
contact email	marc.dieu@unamur.be
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD042613

PRIDE project URI

• PRIDE
  1. PXD042613
     1. Label: PRIDE project
     2. Name: An organ-specific angiogenic control mechanism for endothelial tailoring.