Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma disrupts distal lung differentiation.
The distal epithelium of the developing lung exhibits high-level expression of protein phosphatase 2A (PP2A), a vital signaling enzyme. Here we report the discovery that in the lung, the PP2A regulatory subunit B56gamma is expressed in a discrete developmental period, with the highest protein levels at embryonic day (e) 17, but no detectable protein in the newborn or adult. By in situ hybridization, B56gamma was highly expressed in the distal epithelium of newly forming airways and in mesenchymal cells. In contrast, expression of B56gamma was quite low in the bronchial epithelium and vascular smooth muscle. Transgenic expression of B56gamma using the lung-specific promoter for surfactant protein C (SP-C) resulted in neonatal death. Examination of lungs from SP-C-B56gamma transgenic e18 fetuses revealed proximal airways and normal blood vessels, but the tissue was densely populated with epithelial-type cells and was devoid of normal peripheral lung structure. A component of the Wnt signaling pathway, beta-catenin, was developmentally regulated in the normal lung and was absent in lung tissue from B-56gamma transgenic fetuses. We propose that B56gamma is expressed at a particular stage of lung development to modulate PP2A action on the Wnt/beta-catenin signaling pathway during lung airway morphogenesis.
Everett
Allen D
AD
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. ade5r@virginia.edu
Kamibayashi
Craig
C
Brautigan
David L
DL
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D017403:In Situ Hybridization; D008168:Lung / Q000002:abnormalities* / Q000201:enzymology* / Q000473:pathology; D008171:Lung Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D054648:Protein Phosphatase 2; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D019076:Transgenes; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2