Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition

Katsumi Fumoto, Hisako Takigawa-Imamura, Kenta Sumiyama, Tomoyuki Kaneiwa, Akira Kikuchi

研究成果: Contribution to journalArticle査読

19 被引用数 (Scopus)

抄録

In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicularsaccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages.

本文言語英語
ページ(範囲)151-162
ページ数12
ジャーナルDevelopment (Cambridge)
144
1
DOI
出版ステータス出版済み - 1 1 2017

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学

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