Article

Cited2 is required for fetal lung maturation.

Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Developmental Biology (impact factor: 4.07). 06/2008; 317(1):95-105. DOI:10.1016/j.ydbio.2008.02.019 pp.95-105
Source: PubMed

ABSTRACT 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.

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Keywords

airway epithelial maturation
 
altered differentiation
 
alveolar cell differentiation
 
alveolar type
 
Cebpa promoter
 
Cited2-null fetal lungs
 
Cited2-Tcfap2a/c complex
 
Cited2-Tcfap2c complex controls lung maturation
 
E18.5 Cited2-null lungs
 
lung development
 
mouse development
 
novel therapeutic strategies
 
regulating Cebpa expression
 
respiratory distress syndromes
 
terminal sac formation
 
terminal sac space
 
terminal sac stage
 
type II alveolar epithelial cells
 
type II epithelial cells
 
vascular development