title: Inhibitory morphogens and monopodial branching of the embryonic chicken lung.
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.
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gleghorn
authors.forename: Jiyong
authors.initials: J
authors.lastname: Kwak
authors.forename: Amira L
authors.initials: AL
authors.lastname: Pavlovich
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002642:Chick Embryo; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D055415:Bone Morphogenetic Protein 4; D053773:Transforming Growth Factor beta1