Nephronectin is required to maintain right lung lobar separation during embryonic development

Nephronectin (NPNT) is a basement membrane (BM) protein and a high-affinity ligand of integrin a8b1 required for kidney morphogenesis in mice. In the lung, NPNT also localizes to BMs, but its potential role in pulmonary development has not been investigated. Mice with a floxed Npnt allele were used to generate global knockouts (KOs). The lung parenchyma of KO mice was indistinguishable from wild-type (WT), and lobe fusion did not alter respiratory mechanics in adult KO mice. Cranial and accessory lobes extracted from KO embryonic lungs fused ex vivo when cultured in juxtaposition, with the area of fusion showing loss of the mesothelial marker Wilms tumour. Because a similar pattern of lobe fusion was previously observed in integrin a8 KO embryos, the study results suggest that NPNT signaling through integrin a8, likely in the visceral pleura, maintains right lung lobe separation during embryogenesis.