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Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

ABSTRACT: 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-? (TGF?), 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.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 TGF?1 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; TGF?1 and BMP4 have distinct but reversible effects on the scaling coefficient of the power law.These data suggest that although autocrine inhibition cannot specify monopodial branching, inhibitory morphogens define the dynamics of lung morphogenesis.

SUBMITTER: Gleghorn JP

PROVIDER: S-EPMC3443594 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

Gleghorn Jason P JP Kwak Jiyong J Pavlovich Amira L AL Nelson Celeste M CM

Developmental dynamics : an official publication of the American Association of Anatomists 20120323 5

<h4>Background</h4>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 l ...[more]

PMID: 22410853

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Project description:Some human organs are composed of bifurcated structures. Two simple branching modes-monopodial and dipodial-have been proposed. With monopodial branching, child branches extend from the sidewall of the parent branch. With dipodial branching, the tip of the bronchus bifurcates. However, the branching modes of the human bronchial tree have not been elucidated precisely. A total of 48 samples between Carnegie stage (CS) 15 and CS23 belonging to the Kyoto Collection were used to acquire imaging data with phase-contrast X-ray computed tomography. Bronchial trees of all samples were three-dimensionally reconstructed from the image data. We analyzed the lobar bronchus, segmental bronchus, and subsegmental bronchus. After calculating each bronchus length, we categorized the branching mode of the analyzed bronchi based on whether the parent bronchus was divided after generation of the analyzed bronchi. All lobar bronchi were formed with monopodial branching. Twenty-five bifurcations were analyzed to categorize the branching mode of the segmental and subsegmental bronchi; 22 bifurcations were categorized as monopodial branching, two bifurcations were not categorized as any branching pattern, and the only lingular bronchus that bifurcated from the left superior lobar bronchus was categorized as dipodial branching. The left superior lobar bronchus did not shorten during the period from CS17 or CS18, when the child branch was generated, to CS23. All analyzed bronchi that could be categorized, except for one, were categorized as monopodial branching. The branching modes of the lobar bronchus and segmental bronchus were similar in the mouse lung and human lung; however, the modes of the subsegmental bronchi were different. Furthermore, remodeling, such as shrinkage of the bronchus, was not observed during the analysis period. Our three-dimensional reconstructions allowed precise calculation of the bronchus length, thereby improving the knowledge of branching morphogenesis in the human embryonic lung.

Dataset Information

Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

Publications

Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

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