Epithelial Sheet Folding Induces Lumen Formation by Madin-Darby Canine Kidney Cells in a Collagen Gel |
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| Authors: | Sumire Ishida Ryosuke Tanaka Naoya Yamaguchi Genki Ogata Takeomi Mizutani Kazushige Kawabata Hisashi Haga |
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| Affiliation: | 1. Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.; 2. Research Center for Cooperative Projects, Hokkaido University Graduate School of Medicine, Sapporo, Japan.; University of Cambridge, United Kingdom, |
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| Abstract: | Lumen formation is important for morphogenesis; however, an unanswered question is whether it involves the collective migration of epithelial cells. Here, using a collagen gel overlay culture method, we show that Madin-Darby canine kidney cells migrated collectively and formed a luminal structure in a collagen gel. Immediately after the collagen gel overlay, an epithelial sheet folded from the periphery, migrated inwardly, and formed a luminal structure. The inhibition of integrin-β1 or Rac1 activity decreased the migration rate of the peripheral cells after the sheets folded. Moreover, lumen formation was perturbed by disruption of apical-basolateral polarity induced by transforming growth factor-β1. These results indicate that cell migration and cell polarity play an important role in folding. To further explore epithelial sheet folding, we developed a computer-simulated mechanical model based on the rigidity of the extracellular matrix. It indicated a soft substrate is required for the folding movement. |
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