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bioRxiv · 10.1101/2020.06.24.165795

Reconstituting Stratified Epithelial Branching Morphogenesis by Engineering Cell Adhesion

Wang, S.·Matsumoto, K.·Yamada, K. M.
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Abstract

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 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 {beta}1 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.

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Wang, S., Matsumoto, K., Yamada, K. M.. 2020-06-24. Reconstituting Stratified Epithelial Branching Morphogenesis by Engineering Cell Adhesion. https://doi.org/10.1101/2020.06.24.165795

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