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

Author

Listed:
  • Denise Martinez Alanis

    (The University of Texas MD Anderson Cancer Center)

  • Daniel R. Chang

    (The University of Texas MD Anderson Cancer Center)

  • Haruhiko Akiyama

    (Kyoto University)

  • Mark A. Krasnow

    (Stanford University School of Medicine)

  • Jichao Chen

    (The University of Texas MD Anderson Cancer Center
    Stanford University School of Medicine
    The University of Texas MD Anderson Cancer Center
    Center for Stem Cells and Developmental Biology, The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • Denise Martinez Alanis & Daniel R. Chang & Haruhiko Akiyama & Mark A. Krasnow & Jichao Chen, 2014. "Two nested developmental waves demarcate a compartment boundary in the mouse lung," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4923
    DOI: 10.1038/ncomms4923
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    Cited by:

    1. Kuan Zhang & Erica Yao & Ethan Chuang & Biao Chen & Evelyn Y. Chuang & Pao-Tien Chuang, 2022. "mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Douglas G. Brownfield & Alex Diaz Arce & Elisa Ghelfi & Astrid Gillich & Tushar J. Desai & Mark A. Krasnow, 2022. "Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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