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Patterning and folding of intestinal villi by active mesenchymal dewetting

Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, the numerous finger-like protrusions that are essential for nutrient absorption. However, the molecular and mechanical mechanism...

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Detalles Bibliográficos
Autores principales: Huycke, Tyler R., Miyazaki, Hikaru, Häkkinen, Teemu J., Srivastava, Vasudha, Barruet, Emilie, McGinnis, Christopher S., Kalantari, Ali, Cornwall-Scoones, Jake, Vaka, Dedeepya, Zhu, Qin, Jo, Hyunil, DeGrado, William F., Thomson, Matt, Garikipati, Krishna, Boffelli, Dario, Klein, Ophir D., Gartner, Zev J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326967/
https://www.ncbi.nlm.nih.gov/pubmed/37425793
http://dx.doi.org/10.1101/2023.06.25.546328
Descripción
Sumario:Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, the numerous finger-like protrusions that are essential for nutrient absorption. However, the molecular and mechanical mechanisms driving the initiation and morphogenesis of villi remain a matter of debate. Here, we identify an active mechanical mechanism that simultaneously patterns and folds intestinal villi. We find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. At the cell-level, this occurs through a process dependent upon matrix metalloproteinase-mediated tissue fluidization and altered cell-ECM adhesion. By combining computational models with in vivo experiments, we reveal 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 de-wetting of a thin liquid film.