Bidirectional Wnt signaling between endoderm and mesoderm confer tracheal identity in mouse and human
Bidirectional Wnt signaling between endoderm and mesoderm confer tracheal identity in mouse and human
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内胚层和中胚层之间的双向 Wnt 信号传导赋予小鼠和人类气管身份
DOI：
10.1101/758235
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Mitsuru Morimoto
中科院分区：
文献类型：
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作者：
Keishi Kishimoto;Kana T. Furukawa;Agustin Luz Madrigal;Akira Yamaoka;Chisa Matsuoka;Masanobu Habu;Cantas Alev;Aaron M. Zorn;Mitsuru Morimoto
哺乳动物气管中的周期性软骨和平滑肌结构来源于气管中胚层，气管畸形导致新生儿严重的呼吸缺陷。在这里，我们表明，在中胚层的经典Wnt信号是至关重要的，赋予气管间充质的身份在人类和小鼠。胎鼠中胚层β-catenin缺失导致Tbx 4+气管中胚层缺失和气管软骨发育不全。Tbx 4的表达依赖于内胚层Wnt活性及其下游Wnt配体，但不依赖于已知的Nkx 2。1-介导的呼吸发育，表明内胚层和中胚层之间的双向Wnt信号传导促进气管发育。在小鼠胚胎干细胞（ESC）来源的侧板中胚层（LPM）中，激活Wnt、Bmp信号，重建体内模型，产生含有软骨细胞和平滑肌细胞的气管中胚层。对于人ESC衍生的LPM，需要SHH活化沿着Wnt以产生适当的气管中胚层。总之，这些发现可能有助于开发人类气管组织修复的应用。
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. Loss of β-catenin in fetal mouse mesoderm caused loss of Tbx4+ tracheal mesoderm and tracheal cartilage agenesis. The Tbx4 expression relied on endodermal Wnt activity and its downstream Wnt ligand but independent of known Nkx2. 1-mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Repopulating in vivo model, activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generated tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation was required along with Wnt to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.