Two nested developmental waves demarcate a compartment boundary in the mouse lung

Nat Commun. 2014 May 29;5:3923. doi: 10.1038/ncomms4923.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Bronchi / anatomy & histology
  • Bronchi / embryology*
  • Bronchi / metabolism
  • Cadherins / metabolism
  • Cell Differentiation
  • Glucocorticoids / metabolism
  • Imaging, Three-Dimensional
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins
  • Lung / embryology
  • Lung / metabolism
  • Mice
  • Morphogenesis
  • Peptides / metabolism
  • Pulmonary Alveoli / anatomy & histology
  • Pulmonary Alveoli / embryology*
  • Pulmonary Alveoli / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Uteroglobin / metabolism

Substances

  • Actins
  • Cadherins
  • Glucocorticoids
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • SOXB1 Transcription Factors
  • Scgb1a1 protein, mouse
  • Sftpc protein, mouse
  • Sox2 protein, mouse
  • Uteroglobin

Associated data

  • GEO/GSE56831