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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 151-162 |
| ページ数 | 12 |
| ジャーナル | Development (Cambridge) |
| 巻 | 144 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | 出版済み - 1 1 2017 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Developmental Biology
これを引用
Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition. / Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira.
：: Development (Cambridge), 巻 144, 番号 1, 01.01.2017, p. 151-162.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition
AU - Fumoto, Katsumi
AU - Takigawa-Imamura, Hisako
AU - Sumiyama, Kenta
AU - Kaneiwa, Tomoyuki
AU - Kikuchi, Akira
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85008467942&partnerID=8YFLogxK
U2 - 10.1242/dev.141325
DO - 10.1242/dev.141325
M3 - Article
C2 - 27913639
AN - SCOPUS:85008467942
VL - 144
SP - 151
EP - 162
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 1
ER -