title: Sox17 is required for normal pulmonary vascular morphogenesis.
abstract: The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis.
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Lange
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, and National Institute for Health Research Respiratory Biomedical Research Unit, Southampton General Hospital, United Kingdom.
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Haitchi
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: LeCras
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States.
authors.forename: Anusha
authors.initials: A
authors.lastname: Sridharan
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wert
authors.affiliation: Heart Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: James
authors.affiliation: Bioengineering Sciences Research Group, Faculty of Engineering and the Environment, University of Southampton, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Udell
authors.affiliation: Bioengineering Sciences Research Group, Faculty of Engineering and the Environment, University of Southampton, United Kingdom.
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Thurner
authors.affiliation: Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States. Electronic address: Jeffrey.Whitsett@cchmc.org.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
mesh_terms: D000818:Animals; D001158:Arteries / Q000002:abnormalities; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000378:metabolism; D017353:Gene Deletion; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000098:blood supply* / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011667:Pulmonary Veins / Q000002:abnormalities; D012097:Repressor Proteins / Q000235:genetics; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics
chemical_list: D024002:HMGB Proteins; D012097:Repressor Proteins; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; D051879:Twist-Related Protein 1; C096852:Twist2 protein, mouse
keywords: Dermo1-Cre; Endothelial; Lung; Sox17; Vascular morphogenesis