Raphaël Clément, Postdoctoral fellow, Laboratoire JA Dieudonné, Nice
21 février, 10h30
In mammals, the bronchial tree results from the repeated self-avoiding branching of lung epithelium in the surrounding mesenchyme. This process has long raised the question of developmental mechanisms involved in morphogenesis. While its molecular basis has been extensively studied, the actual branching mechanism and the way branching events are organized at the organ scale remain to be understood through a model compatible with evidenced signalling pathways.
We designed a simple model based on the basic molecular and physical features of lung development. It reveals that the mere diffusion of the principal growth promoter (FGF10) accounts for the expression patterns of downstream genes and for the growth distribution on the epithelium. From there, we developed 2D and 3D simulations where epithelial growth is triggered by FGF10 reception. Starting from a unique epithelial tube, and calculating local growth as a function of FGF10 received through diffusion in the mesenchyme, we found that most of the striking features of the embryonic lung geometry - such as self-avoiding and space-filling branching, branching asymmetry, size dispersion, etc – emerge spontaneously through mechanisms that we detail. Finally, additional results suggest that similar mechanisms may be at play during the morphogenesis of other branched organs.
Our results suggest that self-organization may play a major role in branching organogenesis. They are consistent with available morphometric data and mutant phenotypes, and question the well-accepted scenario of a master genetic routine.