Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus.

Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus.
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DOI:
10.1038/s41467-018-05189-2
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发表时间:
2018-07-19
影响因子:
16.6
通讯作者:
Morimoto M
Morimoto M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kishimoto K;Tamura M;Nishita M;Minami Y;Yamaoka A;Abe T;Shigeta M;Morimoto M

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Tube morphogenesis is essential for internal-organ development, yet the mechanisms regulating tube shape remain unknown. Here, we show that different mechanisms regulate the length and diameter of the murine trachea. First, we found that trachea development progresses via sequential elongation and expansion processes. This starts with a synchronized radial polarization of smooth muscle (SM) progenitor cells with inward Golgi-apparatus displacement regulates tube elongation, controlled by mesenchymal Wnt5a-Ror2 signaling. This radial polarization directs SM progenitor cell migration toward the epithelium, and the resulting subepithelial morphogenesis supports tube elongation to the anteroposterior axis. This radial polarization also regulates esophageal elongation. Subsequently, cartilage development helps expand the tube diameter, which drives epithelial-cell reshaping to determine the optimal lumen shape for efficient respiration. These findings suggest a strategy in which straight-organ tubulogenesis is driven by subepithelial cell polarization and ring cartilage development. Tracheal development arises due to tube morphogenesis but how this is regulated is unclear. Here, the authors identify polarization of smooth muscle progenitors as controlling murine tracheal development, activating noncanonical Wnt signaling followed by subepithelial morphogenesis and ring cartilage development.
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