title: Mechanical Regulation of Three-Dimensional Epithelial Fold Pattern Formation in the Mouse Oviduct.
abstract: Epithelia exhibit various three-dimensional morphologies linked to organ function in animals. However, the mechanisms of three-dimensional morphogenesis remain elusive. The luminal epithelium of the mouse oviduct forms well-aligned straight folds along the longitudinal direction of the tubes. Disruption of the Celsr1 gene, a planar cell polarity-related gene, causes ectopically branched folds. Here, we evaluated the mechanical contributions of the epithelium to the fold pattern formation. In the mutant oviduct, the epithelium was more intricate along the longitudinal direction than in the wild-type, suggesting a higher ratio of the longitudinal length of the epithelial layer to that of the surrounding smooth muscle (SM) layer (L-Epi/SM ratio). Our mathematical modeling and computational simulations suggested that the L-Epi/SM ratio could explain the differences in fold branching between the two genotypes. Longitudinal epithelial tensions were increased in well-aligned folds compared with those in disorganized folds both in the simulations and in experimental estimations. Artificially increasing the epithelial tensions suppressed the branching in simulations, suggesting that the epithelial tensions can regulate fold patterning. The epithelial tensions could be explained by the combination of line tensions along the epithelial cell-cell boundaries with the polarized cell arrays observed in vivo. These results suggest that the fold pattern is associated with the polarized cell array through the longitudinal epithelial tension. Further simulations indicated that the L-Epi/SM ratio could contribute to fold pattern diversity, suggesting that the L-Epi/SM ratio is a critical parameter in the fold patterning in tubular organs.
authors: Division of Embryology, National Institute for Basic Biology, Okazaki, Aichi, Japan; SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, Japan. Electronic address: hkoyama@nibb.ac.jp.
authors: Hiroshi
authors: H
authors: Koyama
authors: Division of Embryology, National Institute for Basic Biology, Okazaki, Aichi, Japan; Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors: Dongbo
authors: D
authors: Shi
authors: SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, Japan; Division of Morphogenesis, National Institute for Basic Biology, Okazaki, Aichi, Japan.
authors: Makoto
authors: M
authors: Suzuki
authors: SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, Japan; Division of Morphogenesis, National Institute for Basic Biology, Okazaki, Aichi, Japan.
authors: Naoto
authors: N
authors: Ueno
authors: Graduate School of Biostudies, Kyoto University, Kyoto, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors: Tadashi
authors: T
authors: Uemura
authors: Division of Embryology, National Institute for Basic Biology, Okazaki, Aichi, Japan; SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. Electronic address: fujimori@nibb.ac.jp.
authors: Toshihiko
authors: T
authors: Fujimori
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004848:Epithelium / Q000378:metabolism*; D005187:Fallopian Tubes / Q000166:cytology* / Q000254:growth & development*; D005260:Female; D055595:Mechanical Phenomena; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D013314:Stress, Mechanical