期刊
BIOLOGY OPEN
卷 1, 期 8, 页码 775-788出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.20121339
关键词
Lung development; Computational biology; Smooth muscles; Vasculogenesis; Branching morphogenesis
类别
资金
- ETH Zurich
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. (C) 2012. Published by The Company of Biologists Ltd.
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