title: Wnt4 is essential to normal mammalian lung development.
abstract: Wnt signaling is essential to many events during organogenesis, including the development of the mammalian lung. The Wnt family member Wnt4 has been shown to be required for the development of kidney, gonads, thymus, mammary and pituitary glands. Here, we show that Wnt4 is critical for proper morphogenesis and growth of the respiratory system. Using in situ hybridization in mouse embryos, we identify a previously uncharacterized site of Wnt4 expression in the anterior trunk mesoderm. This expression domain initiates as early as E8.25 in the mesoderm abutting the tracheoesophageal endoderm, between the fusing dorsal aortae and the heart. Analysis of Wnt4(-/-) embryos reveals severe lung hypoplasia and tracheal abnormalities; however, aortic fusion and esophageal development are unaffected. We find decreased cell proliferation in Wnt4(-/-) lung buds, particularly in tip domains. In addition, we observe reduction of the important lung growth factors Fgf9, Fgf10, Sox9 and Wnt2 in the lung bud during early stages of organogenesis, as well as decreased tracheal expression of the progenitor factor Sox9. Together, these data reveal a previously unknown role for the secreted protein Wnt4 in respiratory system development.
authors: Dept. of Biology and Physical Sciences, Marymount Univ., 2807 N. Glebe Rd., Arlington, VA 22207, USA.
authors: Arianna
authors: A
authors: Caprioli
authors: Developmental Genetics, Max Planck Institute for Heart and Lung Research, Germany.
authors: Alethia
authors: A
authors: Villasenor
authors: Dept. of Genetics, Univ. of North Carolina, Chapel Hill, NC 27599, USA.
authors: Lyndsay A
authors: LA
authors: Wylie
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Caitlin
authors: C
authors: Braitsch
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Leilani
authors: L
authors: Marty-Santos
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: David
authors: D
authors: Barry
authors: Dept. of Orthopaedic Surgery, Washington Univ. School of Medicine, St. Louis, MO 63131, USA.
authors: Courtney M
authors: CM
authors: Karner
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Stephen
authors: S
authors: Fu
authors: Dept. of Cell and Molecular Biology, Tulane Univ., 2000 Percival Stern Hall, New Orleans, LA 70118, USA.
authors: Stryder M
authors: SM
authors: Meadows
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Thomas J
authors: TJ
authors: Carroll
authors: Dept. of Molecular Biology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Electronic address: ondine.cleaver@utsouthwestern.edu.
authors: Ondine
authors: O
authors: Cleaver
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D051525:Fibroblast Growth Factor 9 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051154:Wnt2 Protein / Q000378:metabolism; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C496464:Fgf10 protein, mouse; C496460:Fgf9 protein, mouse; D051526:Fibroblast Growth Factor 10; D051525:Fibroblast Growth Factor 9; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D051154:Wnt2 Protein; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse
keywords: Cell proliferation; Fgf10; Fgf9; Lung development; Trachea; Ttf1; Wnt2; Wnt4