ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels

Jeremiah Bernier-Latmani (), Cristina Mauri, Rachel Marcone, François Renevey, Stephan Durot, Liqun He, Michael Vanlandewijck, Catherine Maclachlan, Suzel Davanture, Nicola Zamboni, Graham W. Knott, Sanjiv A. Luther, Christer Betsholtz, Mauro Delorenzi, Cathrin Brisken and Tatiana V. Petrova ()
Additional contact information
Jeremiah Bernier-Latmani: Ludwig Institute for Cancer Research Lausanne and University of Lausanne
Cristina Mauri: Ludwig Institute for Cancer Research Lausanne and University of Lausanne
Rachel Marcone: SIB Swiss Institute of Bioinformatics
François Renevey: University of Lausanne
Stephan Durot: Institute of Molecular Systems Biology ETH
Liqun He: Uppsala University
Michael Vanlandewijck: Uppsala University
Catherine Maclachlan: School of Life Sciences, EPFL
Suzel Davanture: Ludwig Institute for Cancer Research Lausanne and University of Lausanne
Nicola Zamboni: Institute of Molecular Systems Biology ETH
Graham W. Knott: School of Life Sciences, EPFL
Sanjiv A. Luther: University of Lausanne
Christer Betsholtz: Uppsala University
Mauro Delorenzi: Ludwig Institute for Cancer Research Lausanne and University of Lausanne
Cathrin Brisken: School of Life Sciences, EPFL
Tatiana V. Petrova: Ludwig Institute for Cancer Research Lausanne and University of Lausanne

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract The small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from the early 1970s uncovered unusual spatial organization of small intestinal villus tip blood vessels: their exterior, epithelial-facing side is fenestrated, while the side facing the villus stroma is non-fenestrated, covered by pericytes and harbors endothelial nuclei. Such organization optimizes the absorption process, however the molecular mechanisms maintaining this highly specialized structure remain unclear. Here we report that perivascular LGR5+ villus tip telocytes (VTTs) are necessary for maintenance of villus tip endothelial cell polarization and fenestration by sequestering VEGFA signaling. Mechanistically, unique VTT expression of the protease ADAMTS18 is necessary for VEGFA signaling sequestration through limiting fibronectin accumulation. Therefore, we propose a model in which LGR5+ ADAMTS18+ telocytes are necessary to maintain a “just-right” level and location of VEGFA signaling in intestinal villus blood vasculature to ensure on one hand the presence of sufficient endothelial fenestrae, while avoiding excessive leakiness of the vessels and destabilization of villus tip epithelial structures.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31571-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31571-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31571-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().