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.
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: Rute S Moura; José P Coutinho-Borges; Ana P Pacheco; Paulo O Damota; Jorge Correia-Pinto Journal: PLoS One Date: 2011-03-11 Impact factor: 3.240
Authors: James W Spurlin; Michael J Siedlik; Bryan A Nerger; Mei-Fong Pang; Sahana Jayaraman; Rawlison Zhang; Celeste M Nelson Journal: Development Date: 2019-08-19 Impact factor: 6.868
Authors: Daniel Tzou; James W Spurlin; Amira L Pavlovich; Carolyn R Stewart; Jason P Gleghorn; Celeste M Nelson Journal: Evodevo Date: 2016-05-26 Impact factor: 2.250
Authors: Alice E Stanton; Katharine Goodwin; Aswin Sundarakrishnan; Jacob M Jaslove; Jason P Gleghorn; Amira L Pavlovich; Celeste M Nelson Journal: Front Cell Dev Biol Date: 2021-12-01