An interplay of geometry and signaling enables robust lung branching morphogenesis
| Autor: | Denis Menshykau, Erkan Ünal, Vincent Sapin, Dagmar Iber, Pierre Blanc |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
FGF10
biology Lung branching morphogenesis Geometry Lung bud Parameter space Embryonic stem cell Models Biological Time-Lapse Imaging Mice Negative feedback biology.protein Morphogenesis Animals Hedgehog Proteins Sonic hedgehog Molecular Biology Turing computer Fibroblast Growth Factor 10 Lung Developmental Biology computer.programming_language Signal Transduction |
| Zdroj: | Development (Cambridge, England). 141(23) |
| ISSN: | 1477-9129 |
| Popis: | Early branching events during lung development are stereotyped. Although key regulatory components have been defined, the branching mechanism remains elusive. We have now used a developmental series of 3D geometric datasets of mouse embryonic lungs as well as time-lapse movies of cultured lungs to obtain physiological geometries and displacement fields. We find that only a ligand-receptor-based Turing model in combination with a particular geometry effect that arises from the distinct expression domains of ligands and receptors successfully predicts the embryonic areas of outgrowth and supports robust branch outgrowth. The geometry effect alone does not support bifurcating outgrowth, while the Turing mechanism alone is not robust to noisy initial conditions. The negative feedback between the individual Turing modules formed by fibroblast growth factor 10 (FGF10) and sonic hedgehog (SHH) enlarges the parameter space for which the embryonic growth field is reproduced. We therefore propose that a signaling mechanism based on FGF10 and SHH directs outgrowth of the lung bud via a ligand-receptor-based Turing mechanism and a geometry effect. |
| Databáze: | OpenAIRE |
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