Cited2 is required for fetal lung maturation

Dev Biol. 2008 May 1;317(1):95-105. doi: 10.1016/j.ydbio.2008.02.019. Epub 2008 Feb 26.


Lung maturation at the terminal sac stage of lung development is characterized by a coordinated increase in terminal sac formation and vascular development in conjunction with the differentiation of alveolar type I and type II epithelial cells. The Cited2-Tcfap2a/c complex has been shown to activate transcription of Erbb3 and Pitx2c during mouse development. In this study, we show that E17.5 to E18.5 Cited2-null lungs had significantly reduced terminal sac space due to an altered differentiation of type I and type II alveolar epithelial cells. In addition, E17 Cited2-null lungs exhibited a decrease in the number of apoptotic cells, contributing to the loss in airspace. Consistent with the phenotype, genes associated with alveolar cell differentiation and survival were differentially expressed in Cited2-null fetal lungs compared to those of wild-type littermates. Moreover, expression of Cebpa, a key regulator of airway epithelial maturation, was significantly decreased in Cited2-null fetal lungs. Cited2 and Tcfap2c were present on the Cebpa promoter in E18.5 lungs to activate Cebpa transcription. We propose that the Cited2-Tcfap2c complex controls lung maturation by regulating Cebpa expression. Understanding the function of this complex may provide novel therapeutic strategies for patients with respiratory distress syndromes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian / metabolism
  • Epithelial Cells / metabolism
  • Fetus / metabolism
  • Lung / embryology*
  • Lung / metabolism
  • Mice
  • Promoter Regions, Genetic
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor AP-2 / metabolism


  • CCAAT-Enhancer-Binding Protein-alpha
  • Cited2 protein, mouse
  • DNA-Binding Proteins
  • Repressor Proteins
  • Tfap2c protein, mouse
  • Trans-Activators
  • Transcription Factor AP-2