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Inhibitory morphogens and monopodial branching of the embryonic chicken lung
Author(s) -
Gleghorn Jason P.,
Kwak Jiyong,
Pavlovich Amira L.,
Nelson Celeste M.
Publication year - 2012
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23771
Subject(s) - biology , morphogen , morphogenesis , microbiology and biotechnology , autocrine signalling , anatomy , receptor , genetics , gene
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.