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  An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea

Yin, W., Liontos, A., Koepke, J., Ghoul, M., Mazzocchi, L., Liu, X., et al. (2022). An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea. DEVELOPMENT, 149(3): dev199804. doi:10.1242/dev.199804.

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Yin, Wenguang1, Author              
Liontos, Andreas, Author
Koepke, Janine, Author
Ghoul, Maroua, Author
Mazzocchi, Luciana, Author
Liu, Xinyuan, Author
Lu, Chunyan, Author
Wu, Haoyu, Author
Fysikopoulos, Athanasios, Author
Sountoulidis, Alexandros, Author
Seeger, Werner2, Author              
Ruppert, Clemens, Author
Gunther, Andreas, Author
Stainier, Didier Y. R.1, Author              
Samakovlis, Christos2, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              
2Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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 Abstract: The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.

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 Dates: 2022-02-07
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000759117000011
DOI: 10.1242/dev.199804
PMID: 35112129
 Degree: -

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Title: DEVELOPMENT
Source Genre: Journal
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Pages: - Volume / Issue: 149 (3) Sequence Number: dev199804 Start / End Page: - Identifier: ISSN: 0950-1991