Centrifugal migration of mesenchymal cells in embryonic lung

Authors

  • Lin Shan,

    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
    2. Departments of Pathology, Children's Hospital and Harvard Medical School, Boston, Massachusetts
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    • Drs. Shan, Subramaniam, and Emanuel contributed equally to this paper.

  • Meera Subramaniam,

    1. Department of Medicine, Division of Respiratory Diseases, Children's Hospital and Harvard Medical School, Boston, Massachusetts
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    • Drs. Shan, Subramaniam, and Emanuel contributed equally to this paper.

  • Rodica L. Emanuel,

    1. Department Medicine, Division of Endocrinology, Children's Hospital and Harvard Medical School, Boston, Massachusetts
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    • Drs. Shan, Subramaniam, and Emanuel contributed equally to this paper.

  • Simone Degan,

    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
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  • Pamela Johnston,

    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
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  • Denise Tefft,

    1. Developmental Biology Program, Saban Research Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine and School of Dentistry, Los Angeles, California
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  • David Warburton,

    1. Developmental Biology Program, Saban Research Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine and School of Dentistry, Los Angeles, California
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  • Mary E. Sunday

    Corresponding author
    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
    2. Departments of Pathology, Children's Hospital, Brigham & Women's Hospital, Massachusetts
    3. Harvard Medical School, Boston, Massachusetts
    • Department of Pathology, Duke University Medical Center, Research Drive, Carl 0043, Durham, NC 27710
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Abstract

Murine lung development begins at embryonic day (E) 9.5. Normal lung structure and function depend on the patterns of localization of differentiated cells. Pulmonary mesenchymal cell lineages have been relatively unexplored. Importantly, there has been no prior evidence of clonality of any lung cells. Herein we use a definitive genetic approach to demonstrate a common origin for proximal and distal pulmonary mesenchymal cells. A retroviral library with 3,400 unique inserts was microinjected into the airway lumen of E11.5 lung buds. After 7–11 days of culture, buds were stained for placental alkaline phosphatase (PLAP). Most PLAP+ cells are peribronchial smooth muscle cells, initially localized laterally near the hilum, then migrating down airways to the subpleural region. Laser-capture microdissection and polymerase chain reaction confirm the clonal identities of PLAP+ cells proximally and distally. Our observation of this fundamental process during lung development opens new avenues for investigation of maladaptive mesenchymal responses in lung diseases. Developmental Dynamics 237:750–757, 2008. © 2008 Wiley-Liss, Inc.

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