First Author | Wang S | Year | 2021 |
Journal | Cell | Volume | 184 |
Issue | 14 | Pages | 3702-3716.e30 |
PubMed ID | 34133940 | Mgi Jnum | J:308454 |
Mgi Id | MGI:6728417 | Doi | 10.1016/j.cell.2021.05.015 |
Citation | Wang S, et al. (2021) Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion. Cell 184(14):3702-3716.e30 |
abstractText | Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in the embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required beta1-integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells. |