| First Author | Roos AB | Year | 2012 |
| Journal | Dev Dyn | Volume | 241 |
| Issue | 5 | Pages | 911-23 |
| PubMed ID | 22411169 | Mgi Jnum | J:183888 |
| Mgi Id | MGI:5319466 | Doi | 10.1002/dvdy.23773 |
| Citation | Roos AB, et al. (2012) Airway epithelial cell differentiation during lung organogenesis requires C/EBPalpha and C/EBPbeta. Dev Dyn 241(5):911-23 |
| abstractText | BACKGROUND: CCAAT/enhancer-binding protein (C/EBP)alpha is crucial for lung development and differentiation of the pulmonary epithelium. Conversely, no lung defects have been observed in C/EBPbeta-deficient mice, although C/EBPbeta trans-activate pulmonary genes by binding to virtually identical DNA-sequences as C/EBPalpha. Thus, the pulmonary phenotype of mice lacking C/EBPbeta could be explained by functional replacement with C/EBPalpha. We investigated whether C/EBPalpha and C/EBPbeta have overlapping functions in regulating lung epithelial differentiation during organogenesis. Epithelial differentiation was assessed in mice with a lung epithelial-specific (SFTPC-Cre-mediated) deletion of C/EBPalpha (Cebpa(DeltaLE) ), C/EBPbeta (Cebpb(DeltaLE) ), or both genes (Cebpa(DeltaLE) ; Cebpb(DeltaLE) ). RESULTS: Both Cebpa(DeltaLE) mice and Cebpa(DeltaLE) ; Cebpb(DeltaLE) mice demonstrated severe pulmonary immaturity compared to wild-type littermates, while no differences in lung histology or epithelial differentiation were observed in Cebpb(DeltaLE) mice. In contrast to Cebpa(DeltaLE) mice, Cebpa(DeltaLE) ; Cebpb(DeltaLE) mice also displayed undifferentiated Clara cells with markedly impaired protein and mRNA expression of Clara cell secretory protein (SCGB1A1), compared to wild-type littermates. In addition, ectopic mucus-producing cells were observed in the conducting airways of Cebpa(DeltaLE) ; Cebpb(DeltaLE) mice. CONCLUSIONS: Our findings demonstrate that C/EBPalpha and C/EBPbeta play pivotal, and partly overlapping roles in determining airway epithelial differentiation, with possible implications for tissue regeneration in lung homeostasis and disease. |
