Inhibitory morphogens and monopodial branching of the embryonic chicken lung
Article first published online: 23 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 241, Issue 5, pages 852–862, May 2012
How to Cite
Gleghorn, J. P., Kwak, J., Pavlovich, A. L. and Nelson, C. M. (2012), Inhibitory morphogens and monopodial branching of the embryonic chicken lung. Dev. Dyn., 241: 852–862. doi: 10.1002/dvdy.23771
- Issue published online: 16 APR 2012
- Article first published online: 23 MAR 2012
- Accepted manuscript online: 12 MAR 2012 01:03PM EST
- Manuscript Accepted: 27 FEB 2012
- David and Lucile Packard Foundation
- Alfred P. Sloan Foundation
- NIH. Grant Numbers: GM083997, HL110335
- lateral branching;
- inhibitory morphogen;
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.