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Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis.

Developmental biology | September 14, 2009 |

Li, Changgong | Li, Aimin | Li, Min | Xing, Yiming | Chen, Hongyan | Hu, Lingyan | Tiozzo, Caterina | Anderson, Stewart | Taketo, Makoto Mark | Minoo, Parviz
Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Abstract

The precise mechanisms by which beta-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development a ... and ciliated, but not basal cell differentiation. Thus, excess beta-catenin can alter cell fate determination by both direct and paracrine mechanisms.

The precise mechanisms by which beta-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development as a model, we deleted exon 3 of beta-catenin via Nkx2.1-cre in the Catnb[+/lox(ex3)] mice and studied its impact on epithelial morphogenesis. Robust selective accumulation of truncated, stabilized beta-catenin was found in Nkx2.1-cre;Catnb[+/lox(ex3)] lungs that were associated with the formation of polyp-like structures in the trachea and main-stem bronchi. Characterization of polyps suggests that accumulated beta-catenin impacts epithelial morphogenesis in at least two ways. "Intracellular" accumulation of beta-catenin blocked differentiation of spatially-appropriate airway epithelial cell types, Clara cells, ciliated cells and basal cells, and activated UCHL1, a marker for pulmonary neuroendocrine cells. There was also evidence for a "paracrine" impact of beta-catenin accumulation, potentially mediated via activation of Bmp4 that inhibited Clara and ciliated, but not basal cell differentiation. Thus, excess beta-catenin can alter cell fate determination by both direct and paracrine mechanisms.

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Nihms-134571-f0001
Fig 1. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0001
Fig 1. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 1

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Nihms-134571-f0004
Fig 2. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0004
Fig 2. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 2

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Nihms-134571-f0005
Fig 3. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0005
Fig 3. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 3

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Nihms-134571-f0007
Fig 4. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0007
Fig 4. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 4

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Nihms-134571-f0008
Fig 5. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0008
Fig 5. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 5

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Nihms-134571-f0010
Fig 6. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0010
Fig 6. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 6

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Nihms-134571-f0011
Fig 7. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0011
Fig 7. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 7

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Nihms-134571-f0014
Fig 8. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0014
Fig 8. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 8

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Nihms-134571-f0016
Fig 9. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0016
Fig 9. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 9

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Nihms-134571-f0018
Fig 10. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0018
Fig 10. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 10

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Fig 11. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.
Nihms-134571-f0020
Fig 11. Li, Li, et al. "Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis." Developmental biology 334.1 (2009): 97-108. Web.

Fig 11

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