Epithelial-mesenchymal interactions during lung development require extracellular signaling factors that facilitate branching morphogenesis. We show here that matrix metalloproteinases (MMPs) originating in the mesenchyme are necessary for epithelial branching and alveolization. We found that the delayed lung maturation characterized by abnormal branching and poor alveolization seen in @entity19 deficient in @entity12841 ( @entity12841 (-/-)) is accompanied by aberrant expression of MMPs. By in situ zymography, the lungs from newborn @entity12841 (-/-) @entity19 had low gelatinolytic activity compared with wildtype. Inhibition of MMPs in developing lungs in vivo or in vitro severely retarded morphogenesis. @entity12841 (-/-) @entity19 had low expression of @entity5781 / @entity5781 , which is a potent activator of @entity5780 / @entity5780 , in their lungs. Egf ligand increased @entity5781 mRNA by tenfold in lung fibroblasts from wild type, but not from @entity12841 (-/-) @entity19 . Extracts from lungs of @entity12841 (-/-) @entity19 showed a tenfold reduction in active @entity5780 , but only a slight decrease in proMMP-2 by zymography. At birth, @entity5780 (-/-) @entity19 had a lung phenotype characterized by abnormal lung alveolization which phenocopied that of @entity12841 (-/-) @entity19 , albeit somewhat less severe. We conclude that proteolysis mediates epithelial/mesenchymal interactions during lung morphogenesis. From the phenotypes of the @entity12841 (-/-) @entity19 , we identify @entity5781 as a major downstream target of @entity12841 signaling in lung in vivo and in vitro. @entity5781 is, in turn, necessary for activation of @entity5780 , a mesenchymal enzyme that is required for normal lung morphogenesis.

Signaling through the EGF receptor controls lung morphogenesis in part by regulating XXXX -mediated activation of @entity5780 / @entity5780 .

@entity19 :: ('10090', 'Species') :: ['mice'] @entity5780 :: ('17390(Tax:10090)', 'Gene') :: ['MMP-2', 'MMP2', 'gelatinase A'] @entity5781 :: ('17387(Tax:10090)', 'Gene') :: ['MMP14', 'MT1-MMP'] @entity12841 :: ('13649(Tax:10090)', 'Gene') :: ['Egfr', 'epidermal growth factor receptor']
@entity5781 :: (17387(Tax:10090),Gene) :: ['MT1-MMP']
