Patterning and folding of intestinal villi by active mesenchymal dewetting.
Cell
; 187(12): 3072-3089.e20, 2024 Jun 06.
Article
in En
| MEDLINE
| ID: mdl-38781967
ABSTRACT
Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Extracellular Matrix
/
Intestinal Mucosa
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2024
Document type:
Article