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

作者：Li Changgong^*; Li Aimin; Li Min; Xing Yiming; Chen Hongyan; Hu Lingyan; Tiozzo Caterina; Anderson Stewart; Taketo Makoto Mark; Minoo Parviz

来源：Developmental Biology, 2009, 334(1): 97-108.

DOI：10.1016/j.ydbio.2009.07.021

• beta-catenin
• Stabilized
• Wnt
• Nkx2.1
• UCHL1
• Polyposis
• Lung development
• Cell fate

The precise mechanisms by which beta-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development as amodel, 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.

• 出版日期2009-10-1