Inhibitory morphogens and monopodial branching of the embryonic chicken lung

Authors

  • Jason P. Gleghorn,

    1. Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey
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  • Jiyong Kwak,

    1. Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey
    Current affiliation:
    1. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
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  • Amira L. Pavlovich,

    1. Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey
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  • Celeste M. Nelson

    Corresponding author
    1. Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey
    2. Department of Molecular Biology, Princeton University, Princeton, New Jersey
    • A321 Engineering Quadrangle, Princeton, NJ 08544
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Abstract

Background: Branching morphogenesis generates a diverse array of epithelial patterns, including dichotomous and monopodial geometries. Dichotomous branching can be instructed by concentration gradients of epithelial-derived inhibitory morphogens, including transforming growth factor-β (TGFβ), which is responsible for ramification of the pubertal mammary gland. Here, we investigated the role of autocrine inhibitory morphogens in monopodial branching morphogenesis of the embryonic chicken lung. Results: Computational modeling and experiments using cultured organ explants each separately revealed that monopodial branching patterns cannot be specified by a single epithelial-derived autocrine morphogen gradient. Instead, signaling by means of TGFβ1 and bone morphogenetic protein-4 (BMP4) differentially affect the rates of branching and growth of the airways. Allometric analysis revealed that development of the epithelial tree obeys power-law dynamics; TGFβ1 and BMP4 have distinct but reversible effects on the scaling coefficient of the power law. Conclusions: These data suggest that although autocrine inhibition cannot specify monopodial branching, inhibitory morphogens define the dynamics of lung morphogenesis. Developmental Dynamics 241:852–862, 2012. © 2012 Wiley Periodicals, Inc.

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