ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels.
Date
2022-07-09ICR Author
Author
Bernier-Latmani, J
Mauri, C
Marcone, R
Renevey, F
Durot, S
He, L
Vanlandewijck, M
Maclachlan, C
Davanture, S
Zamboni, N
Knott, GW
Luther, SA
Betsholtz, C
Delorenzi, M
Brisken, C
Petrova, TV
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Duodenum
Intestinal Mucosa
Intestines
Nutrients
Telocytes
Research team
Endocrine control mechans
Language
eng
Date accepted
2022-06-21
License start date
2022-07-09
Citation
Nature Communications, 2022, 13 (1), pp. 3983 -
Publisher
NATURE PORTFOLIO