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

Keishi Kishimoto,Takaya Abe,Mayo Shigeta,Mitsuru Morimoto,Masaru Tamura,Yasuhiro Minami,Akira Yamaoka,Michiru Nishita

doi:10.1038/s41467-018-05189-2

Keishi Kishimoto, Takaya Abe + Show 6 more

Open Access

https://doi.org/10.1038/s41467-018-05189-2

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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.

Highlights

Tube morphogenesis is essential for internal-organ development, yet the mechanisms regulating tube shape remain unknown
The luminal-surface area of the developing trachea was measured by a combination of high-resolution micro-computed tomography scanning and 3D-image analysis (Fig. 1f–i and Supplementary Movie 1)
To investigate the mechanism underlying the luminal-surface enlargement that occurs with a low proliferation rate in trachea tubulogenesis phase 2, we examined the cell morphology and alignment of the developing epithelium in detail

Summary

Introduction

Tube morphogenesis is essential for internal-organ development, yet the mechanisms regulating tube shape remain unknown. 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-Ror[2] signaling. This radial polarization directs SM progenitor cell migration toward the epithelium, and the resulting subepithelial morphogenesis supports tube elongation to the anteroposterior axis. 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. The mechanisms underlying tracheal tubulogenesis after the initial separation are poorly understood

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Conclusion