Wnt5a-Vangl1/2 signaling regulates the position and direction of lung branching through the cytoskeleton and focal adhesions.
Wnt5a-Vangl1/2 signaling regulates the position and direction of lung branching through the cytoskeleton and focal adhesions.
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DOI：
10.1371/journal.pbio.3001759
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发表时间：
2022-08
期刊：
影响因子：
9.8
通讯作者：
Chuang, Pao-Tien
中科院分区：
文献类型：
--
作者：
Zhang, Kuan;Yao, Erica;Chuang, Ethan;Chen, Biao;Chuang, Evelyn Y.;Volk, Regan F.;Hofmann, Katherine L.;Zaro, Balyn;Chuang, Pao-Tien
肺分支形态发生需要上皮和间充质之间的相互作用。如何在定义的位置生成肺分支并向特定方向投影仍然是一个尚未解决的主要问题。在这项研究中，我们研究了Wnt信号在小鼠肺分支中的功能。我们发现，上皮和间充质中的Wnt 5a在控制肺分支的位置和方向中起着至关重要的作用。Wnt 5a信号由Vangl 1/2介导，触发非经典或平面细胞极性（PCP）信号传导的级联反应。响应于非经典Wnt信号传导，肺细胞经历细胞骨架重组并改变粘着斑。肺移植物中的扰动局灶性粘连与分支缺陷有关。此外，我们观察到的形状和方向的上皮片和下面的间充质层的缺陷分支在突变体肺的区域的变化。因此，PCP信号有助于定义肺分支的位置和方向。我们提出，机械力诱导的非经典Wnt信号介导的一组上皮细胞和间充质细胞的形状和方向的协调改变。这些结果提供了一个新的框架，了解的分子机制，其中产生的刻板的分支模式。肺分支形态发生需要上皮和间充质之间的相互作用，但这些分支是如何在确定的位置和方向产生的？这项研究表明，非典型的Wnt 5a信号转导导致肺细胞骨架和局灶性粘连的变化，由此改变的上皮片的形状和方向有助于确定肺分支的位置和方向。
Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme. How the lung branches are generated at a defined location and projected toward a specific direction remains a major unresolved issue. In this study, we investigated the function of Wnt signaling in lung branching in mice. We discovered that Wnt5a in both the epithelium and the mesenchyme plays an essential role in controlling the position and direction of lung branching. The Wnt5a signal is mediated by Vangl1/2 to trigger a cascade of noncanonical or planar cell polarity (PCP) signaling. In response to noncanonical Wnt signaling, lung cells undergo cytoskeletal reorganization and change focal adhesions. Perturbed focal adhesions in lung explants are associated with defective branching. Moreover, we observed changes in the shape and orientation of the epithelial sheet and the underlying mesenchymal layer in regions of defective branching in the mutant lungs. Thus, PCP signaling helps define the position and orientation of the lung branches. We propose that mechanical force induced by noncanonical Wnt signaling mediates a coordinated alteration in the shape and orientation of a group of epithelial and mesenchymal cells. These results provide a new framework for understanding the molecular mechanisms by which a stereotypic branching pattern is generated. Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme, but how are these branches are generated at a defined location and orientation? This study reveals that non-canonical Wnt5a signaling causes changes in lung cell cytoskeleton and focal adhesions, and the resulting altered shape and orientation of the epithelial sheet helps define the position and orientation of lung branches.
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影响因子：
--
作者：
Carroll TJ;Yu J
通讯作者：
Yu J
影响因子：
5.5
作者：
Jones MR;Chong L;Bellusci S
通讯作者：
Bellusci S
影响因子：
16.6
作者：
Kishimoto K;Tamura M;Nishita M;Minami Y;Yamaoka A;Abe T;Shigeta M;Morimoto M
通讯作者：
Morimoto M
影响因子：
4.8
作者：
Slack-Davis, Jill K.;Martin, Karen H.;Parsons, J. Thomas
通讯作者：
Parsons, J. Thomas
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B