Alveologenesis requires the coordinated modulation of the epithelial and mesenchymal compartments to generate mature alveolar saccules for efficient gas exchange. However, the molecular mechanisms underlying the epithelial-mesenchymal interaction during alveologenesis are poorly understood. Here, we report that Wnts produced by epithelial cells are critical for neonatal alveologenesis. Deletion of the Wnt chaperon protein Wntless homolog (Wls) disrupts alveolar formation, resulting in enlarged saccules in Sftpc-Cre/Nkx2.1-Cre; Wlsloxp/loxp mutants. Although commitment of the alveolar epithelium is unaffected, α-SMA+ mesenchymal cells persist in the alveoli accompanied by increased collagen deposition and mutants exhibit exacerbated fibrosis following bleomycin challenge. Notably, α-SMA+ cells include a significant number of endothelial cells resembling endothelial to mesenchymal transition (EndMT) which is also present in Ager-CreER; Wlsloxp/loxp mutants following early postnatal Wls deletion. These findings provide initial evidence that epithelial-derived Wnts are critical for the differentiation of the surrounding mesenchyme during early postnatal alveologenesis.
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RESEARCH REPORT|
21 December 2021
Epithelial Wntless (Wls) regulates postnatal alveologenesis
Yinshan Fang
,
Yinshan Fang
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
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Hongxia Shao
,
Hongxia Shao
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
2
Tianjin Haihe Hospital, Tianjin, Tianjin 300350
, China
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Qi Wu
,
Qi Wu
2
Tianjin Haihe Hospital, Tianjin, Tianjin 300350
, China
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Neng Chun Wong,
Neng Chun Wong
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
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Natalie Tsong
,
Natalie Tsong
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
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Patricia Sime
,
Patricia Sime
3
Department of Internal Medicine, Virginia Commonwealth University in Richmond, Richmond, VA 23298
, USA
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Jianwen Que
Jianwen Que
*
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
*Author for correspondence: jq2240@cumc.columbia.edu
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Yinshan Fang
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
Hongxia Shao
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
2
Tianjin Haihe Hospital, Tianjin, Tianjin 300350
, China
2
Tianjin Haihe Hospital, Tianjin, Tianjin 300350
, China
Neng Chun Wong
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
Natalie Tsong
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
Patricia Sime
3
Department of Internal Medicine, Virginia Commonwealth University in Richmond, Richmond, VA 23298
, USA
Jianwen Que
*
1
Division of Digestive and Liver Diseases, Department of Medicine, USA; Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032
, USA
*Author for correspondence: jq2240@cumc.columbia.edu
Received:
08 Feb 2021
Accepted:
09 Dec 2021
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Funding Group:
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): R01HL152293
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): NIH Office of the Director
- Award Id(s): S10RR027050
- Funder(s):
Development dev.199505.
Article history
Received:
08 Feb 2021
Accepted:
09 Dec 2021
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Citation
Yinshan Fang, Hongxia Shao, Qi Wu, Neng Chun Wong, Natalie Tsong, Patricia Sime, Jianwen Que; Epithelial Wntless (Wls) regulates postnatal alveologenesis. Development 2021; dev.199505. doi: https://doi.org/10.1242/dev.199505
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