Simulations demonstrate a simple network to be sufficient to control
branch point selection, smooth muscle and vasculature formation during lung
branching morphogenesis
Proper lung functioning requires not only a correct structure of the
conducting airway tree, but also the simultaneous development of smooth muscles
and vasculature. Lung branching morphogenesis is strongly stereotyped and
involves the recursive use of only three modes of branching. We have previously
shown that the experimentally described interactions between Fibroblast growth
factor (FGF)10, Sonic hedgehog (SHH) and Patched (Ptc) can give rise to a
Turing mechanism that not only reproduces the experimentally observed wildtype
branching pattern but also, in part counterintuitive, patterns in mutant mice.
Here we show that, even though many proteins affect smooth muscle formation and
the expression of Vegfa, an inducer of blood vessel formation, it is sufficient
to add FGF9 to the FGF10/SHH/Ptc module to successfully predict simultaneously
the emergence of smooth muscles in the clefts between growing lung buds, and
Vegfa expression in the distal sub-epithelial mesenchyme. Our model reproduces
the phenotype of both wildtype and relevant mutant mice, as well as the results
of most culture conditions described in the literature.Comment: Initially published at Biology Ope
