GATA-6 is required for maturation of the lung in late gestation.
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-alpha staining, both markers of type I cells, were decreased. Homogeneous 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.
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Cong
C
Liu
Edward E
EE
Morrisey
Jeffrey A
JA
Whitsett
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D050993:GATA6 Transcription Factor; D018398:Homeodomain Proteins / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C106185:engrailed homeobox proteins