title: Two nested developmental waves demarcate a compartment boundary in the mouse lung.
abstract: The lung is a branched tubular network with two distinct compartments--the proximal conducting airways and the peripheral gas exchange region--separated by a discrete boundary termed the bronchoalveolar duct junction (BADJ). Here we image the developing mouse lung in three-dimensions (3D) and show that two nested developmental waves demarcate the BADJ under the control of a global hormonal signal. A first wave of branching morphogenesis progresses throughout embryonic development, generating branches for both compartments. A second wave of conducting airway differentiation follows the first wave but terminates earlier, specifying the proximal compartment and setting the BADJ. The second wave is terminated by a glucocorticoid signalling: premature activation or loss of glucocorticoid signalling causes a proximal or distal shift, respectively, in BADJ location. The results demonstrate a new mechanism of boundary formation in complex, 3D organs and provide new insights into glucocorticoid therapies for lung defects in premature birth.
authors.affiliation: 1] Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
authors.forename: Denise Martinez
authors.initials: DM
authors.lastname: Alanis
authors.affiliation: 1] Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Chang
authors.affiliation: Department of Orthopedics, Kyoto University, Sakyo, Kyoto 606-8507, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Biochemistry and HHMI, Stanford University School of Medicine, Stanford, California 94305-5307, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Krasnow
authors.affiliation: 1] Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Biochemistry and HHMI, Stanford University School of Medicine, Stanford, California 94305-5307, USA [3] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [4] Center for Stem Cells and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jichao
authors.initials: J
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D005938:Glucocorticoids / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D010455:Peptides / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D055748:SOXB1 Transcription Factors; C556390:Scgb1a1 protein, mouse; C489680:Sftpc protein, mouse; C527783:Sox2 protein, mouse; D014598:Uteroglobin