{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:02:18Z","timestamp":1790942538387,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"40","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,10,5]]},"abstract":"<jats:p>\n                    Toward the end of gestation in mammals, the fetal lung undergoes a process of differentiation that is required for transition to air breathing at birth. Respiratory epithelial cells synthesize the surfactant proteins and lipids that together form the pulmonary surfactant complex necessary for lung function. Failure of this process causes respiratory distress syndrome, a leading cause of perinatal death and morbidity in newborn infants. Here we demonstrate that expression of the forkhead gene\n                    <jats:italic>Foxa2<\/jats:italic>\n                    in respiratory epithelial cells of the peripheral lung controls pulmonary maturation at birth. Newborn mice lacking\n                    <jats:italic>Foxa2<\/jats:italic>\n                    expression in the lung develop severe pulmonary disease on the first day of life, with all of the morphological, molecular, and biochemical features of respiratory distress syndrome in preterm infants, including atelectasis, hyaline membranes, and the lack of pulmonary surfactant lipids and proteins. RNA microarray analysis at embryonic day 18.5 demonstrated that Foxa2-regulated expression of a group of genes mediating surfactant protein and lipid synthesis, host defense, and antioxidant production.\n                    <jats:italic>Foxa2<\/jats:italic>\n                    regulates a complex pulmonary program of epithelial cell maturation required for transition to air breathing at birth.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0404424101","type":"journal-article","created":{"date-parts":[[2004,9,27]],"date-time":"2004-09-27T20:14:42Z","timestamp":1096316082000},"page":"14449-14454","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["<i>Foxa2<\/i>\n                    is required for transition to air breathing at birth"],"prefix":"10.1073","volume":"101","author":[{"given":"Huajing","family":"Wan","sequence":"first","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiko","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mildred T.","family":"Stahlman","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus H.","family":"Kaestner","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew-Lan","family":"Ang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Whitsett","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2370; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145; and Division of Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, England"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,9,27]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"517","volume":"97","year":"1959","unstructured":"Avery, M. 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