title: Epithelial sheet folding induces lumen formation by Madin-Darby canine kidney cells in a collagen gel.
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.
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Sumire
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Ogata
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Takeomi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawabata
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan; Research Center for Cooperative Projects, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
mesh_terms: D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry*; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D039641:Integrin beta Chains / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008954:Models, Biological
chemical_list: D005782:Gels; D039641:Integrin beta Chains; D003094:Collagen