Inhibitory morphogens and monopodial branching of the embryonic chicken lung

Jason P. Gleghorn, Jiyong Kwak, Amira L. Pavlovich, Celeste M. Nelson

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)852-862
Number of pages11
JournalDevelopmental Dynamics
Volume241
Issue number5
DOIs
StatePublished - May 2012

All Science Journal Classification (ASJC) codes

  • Developmental Biology

Keywords

  • Allometry
  • Inhibitory morphogen
  • Lateral branching
  • Morphodynamics
  • Patterning

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