2013.10.16 熊本大学リエゾンラボ研究会

熊本大学でセミナーを行いました．

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Mechanism of lung branching morphogenesis

Human airway has tree-like structure. This structure is generated by repeated tip splitting during development, which is called branching morphogenesis. This process is thought be the result of complex epithelial-mesenchymal interaction, and various molecules are known to be involved in this process. However, how the interactions of these molecules result in branching morphogenesis remain to be elucidated.

At first we utilized mesenchyme-free system to understand the process. In this culture system, isolated lung epithelium cultured in Matrigel form branched structure spontaneously. In this culture system, fibroblast growth factor (FGF) is necessary to induce the branched structure. Combining mathematical modeling and experiment, we formulated two-species reaction diffusion model that can reproduce and predict most of the known experimental results.

Next we try to model the epithelial-mesenchymal interaction during lung development in vivo. By simplifying the known molecular network, we can model the complex molecular interaction by interface equation coupled with convolution kernel. The model is simple enough to derive various morphological characteristics mathematically, and also can reproduce various experimental results. We are now trying to experimentally verify the model by visualizing morphogen diffusion dynamics in lung mesenchyme.

References:
1. Miura, T. et al. The cyst-branch difference in developing chick lung results from a different morphogen diffusion coefficient. Mech Dev 126, 160–172 (2009).
2. Miura, T. Modeling Lung Branching Morphogenesis. Current topics in developmental biology 81, 291–310 (2008).
3. Miura, T. & Shiota, K. Depletion of FGF acts as a lateral inhibitory factor in lung branching morphogenesis in vitro. Mech Dev 116, 29–38 (2002).