The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

摘要: The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation either correct number or shape epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such cystadenomatoid malformations, pulmonary hypertension hypoplasia. Defects architecture also associated with adult disease, particularly cases idiopathic fibrosis. Identifying pathways which drive tube will likely shed light on both disease. Here we show mutations planar cell polarity (PCP) genes Celsr1 Vangl2 disrupted development defects architecture. Lungs from Crsh Lp mouse mutants small misshapen fewer branches, late gestation exhibit thickened interstitial defective saccular formation. We observe recapitulation these following inhibition Rho kinase, an important downstream effector PCP pathway. Moreover, integrity is disrupted, cytoskeletal remodelling perturbed mutant endoderm does not branch normally response chemoattractant FGF10. further proteins present restricted spatial domains within epithelium. Our data required for foetal thereby revealing novel pathway critical this process enhance our understanding diseases may future therapeutic strategies.