中胚层
内胚层
Wnt信号通路
细胞生物学
节的
FGF与中胚层形成
生物
胚芽层
侧板中胚层
外胚层
胚胎发生
解剖
细胞分化
胚胎
胚胎干细胞
信号转导
遗传学
诱导多能干细胞
基因
作者
Keishi Kishimoto,Kana T. Furukawa,Agustín Luz-Madrigal,Akira Yamaoka,Chisa Matsuoka,Masanobu Habu,Cantas Alev,Aaron M. Zorn,Mitsuru Morimoto
标识
DOI:10.1038/s41467-020-17969-w
摘要
Abstract The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory defects in neonates. Here we show that canonical Wnt signaling in mesoderm is critical to confer trachea mesenchymal identity in human and mouse. At the initiation of tracheal development, endoderm begins to express Nkx2.1 , and then mesoderm expresses the Tbx4 gene. Loss of β-catenin in fetal mouse mesoderm causes loss of Tbx4 + tracheal mesoderm and tracheal cartilage agenesis. The mesenchymal Tbx4 expression relies on endodermal Wnt activation and Wnt ligand secretion but is independent of known Nkx2.1 -mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generates tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation is required along with WNT to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.
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