In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 8 ( 2022-8-26), p. e3001759-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001759
DOI:
10.1371/journal.pbio.3001759.g001
DOI:
10.1371/journal.pbio.3001759.g002
DOI:
10.1371/journal.pbio.3001759.g003
DOI:
10.1371/journal.pbio.3001759.g004
DOI:
10.1371/journal.pbio.3001759.s001
DOI:
10.1371/journal.pbio.3001759.s002
DOI:
10.1371/journal.pbio.3001759.s003
DOI:
10.1371/journal.pbio.3001759.s004
DOI:
10.1371/journal.pbio.3001759.s005
DOI:
10.1371/journal.pbio.3001759.s006
DOI:
10.1371/journal.pbio.3001759.s007
DOI:
10.1371/journal.pbio.3001759.s008
DOI:
10.1371/journal.pbio.3001759.s009
DOI:
10.1371/journal.pbio.3001759.s010
DOI:
10.1371/journal.pbio.3001759.s011
DOI:
10.1371/journal.pbio.3001759.s012
DOI:
10.1371/journal.pbio.3001759.s013
DOI:
10.1371/journal.pbio.3001759.s014
DOI:
10.1371/journal.pbio.3001759.s015
DOI:
10.1371/journal.pbio.3001759.s016
DOI:
10.1371/journal.pbio.3001759.s017
DOI:
10.1371/journal.pbio.3001759.r001
DOI:
10.1371/journal.pbio.3001759.r002
DOI:
10.1371/journal.pbio.3001759.r003
DOI:
10.1371/journal.pbio.3001759.r004
DOI:
10.1371/journal.pbio.3001759.r005
DOI:
10.1371/journal.pbio.3001759.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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