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

Keishi Kishimoto, Masaru Tamura, Michiru Nishita, Yasuhiro Minami, Akira Yamaoka, Takaya Abe, Mayo Shigeta and Mitsuru Morimoto ()
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Keishi Kishimoto: RIKEN Center for Developmental Biology
Masaru Tamura: RIKEN BioResource Center
Michiru Nishita: Kobe University
Yasuhiro Minami: Kobe University
Akira Yamaoka: RIKEN Center for Developmental Biology
Takaya Abe: Center for Biosystems Dynamics Research
Mayo Shigeta: Center for Biosystems Dynamics Research
Mitsuru Morimoto: RIKEN Center for Developmental Biology

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05189-2

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