Simulations demonstrate a simple network to be sufficient to control branch point selection, smooth muscle and vasculature formation during lung branching morphogenesis

摘要

Proper lung functioning requires not only a correct structure of theconducting airway tree, but also the simultaneous development of smooth musclesand vasculature. Lung branching morphogenesis is strongly stereotyped andinvolves the recursive use of only three modes of branching. We have previouslyshown that the experimentally described interactions between Fibroblast growthfactor (FGF)10, Sonic hedgehog (SHH) and Patched (Ptc) can give rise to aTuring mechanism that not only reproduces the experimentally observed wildtypebranching pattern but also, in part counterintuitive, patterns in mutant mice.Here we show that, even though many proteins affect smooth muscle formation andthe expression of Vegfa, an inducer of blood vessel formation, it is sufficientto add FGF9 to the FGF10/SHH/Ptc module to successfully predict simultaneouslythe emergence of smooth muscles in the clefts between growing lung buds, andVegfa expression in the distal sub-epithelial mesenchyme. Our model reproducesthe phenotype of both wildtype and relevant mutant mice, as well as the resultsof most culture conditions described in the literature.