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1 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039; and 2 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
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 embryonic day (E)
6-7 by treatment of the dam with doxycycline. Although branching morphogenesis of the proximal airways proceeded normally to
E16.5, maturation of terminal airways and alveoli that
normally occurs before birth was inhibited. At
E17.5-18.5, aquaporin-5 mRNA and type I cell
marker-
staining, both markers of type I cells, were
decreased. Homogenous distribution of the thyroid transcription
factor-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 before birth.
lung development; transcription factors
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