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Articles in PresS, published online ahead of print March 22, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00044.2002
Submitted on January 29, 2002
Accepted on March 15, 2002
1 Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH, USA
2 Medicine, University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: jeff.whitsett{at}chmcc.org.
GATA-6, a member of the GATA family of zinc finger proteins, is the only family member known to be expressed in the epithelial cells of the developing airway epithelium. To determine the role of GATA-6 in lung morphogenesis, a chimeric fusion protein containing GATA-6 and the strong transcriptional inhibitor, engrailed, was conditionally expressed in mice under control of a doxycycline inducible transgene. Expression of GATA-6-engrailed was initiated at E6-7 by treatment of the dam with doxycycline. While branching morphogenesis of the proximal airways proceeded normally to E16.5, maturation of terminal airways and alveoli that normally occurs prior to birth was inhibited. At E17.5-18.5, aquaporin-5 mRNA and T1
staining, both markers of type I cells, were decreased. Homogenous distribution of the transcription factor TTF-1, decreased expression of surfactant proteins, delayed thinning of the walls of the peripheral airways, and lack of squamous differentiation of epithelial cells were observed in the lung periphery after expression of GATA-6-engrailed. Activity of GATA-6 is required for maturation of the gas exchange area prior to birth.
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