@article {68137,
	title = {Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion},
	journal = {Cell},
	volume = {184},
	year = {2021},
	pages = {3702-3716.e30},
	abstract = {<p>Summary 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 β1-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.</p>
},
	keywords = {branching morphogenesis, budding morphogenesis, cell-cell adhesion, cell-matrix adhesion, differential adhesion, E-cadherin, epithelial morphogenesis, integrin, salivary gland, tissue engineering},
	issn = {0092-8674},
	doi = {https://doi.org/10.1016/j.cell.2021.05.015},
	url = {https://www.sciencedirect.com/science/article/pii/S0092867421006322},
	author = {Shaohe Wang and Kazue Matsumoto and Samantha R. Lish and Alexander X. Cartagena-Rivera and Kenneth M. Yamada}
}
