Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice
J. Clin. Invest. Shigehisa Yanagi, et al. 117:2929 doi:10.1172/JCI31854 [Go to this article.]

Figure 2
Abnormal thickness of the blood-air barrier and impaired alveolar epithelial cell differentiation in SOPten^flox/flox(E10–E16) lungs. (A) Transmission electron micrographs of the lung septa of E19.5 embryos shown at low (LM) and high (HM) magnification. WT(E10–E16) lung showed AE-I and AE-II cells plus 2 layers of capillaries (asterisks) separated by mesenchymal cells (M; upper left panel). The AE-II cells contained many lamellar bodies (white arrowheads) and apical microvilli (lower left panel). SPs (arrow) were visible in the saccular spaces (upper left panel). Black arrowheads (left panels) indicate the thin, normal blood-air barrier, composed of AE-I cells and capillary endothelial cells, in the WT lung. In the SOPten^flox/flox(E10–E16) lung, the septa were thick with increased mesenchymal cells (upper right panel). Increased numbers of undifferentiated cuboidal epithelial cells of enlarged size were present (CC; upper right panel). The blood-air barrier (red bars) was significantly thicker in SOPten^flox/flox lungs than in WT lungs (lower panels). Scale bars: 10 μm (LM); 5 μm (HM). (B and C) Altered marker protein expression. (B) Western blotting of SP-A, -B, -C, -D, AQP5, and CCSP proteins in extracts of whole lungs taken from WT(E10–E16) and SOPten^flox/flox(E10–E16) mice at E19.5. Actin was used as a loading control. Data shown are representative of 3 trials. (C) IHC analysis of SP-C, AQP5, CCSP and CGRP. SP-C and AQP5 immunostaining was intense in cuboidal AE-II and flat AE-I cells, respectively, in WT(E10–E16) lungs at E19.5 but dramatically decreased in SOPten^flox/flox(E10–E16) lung at E19.5. Scale bars: 50 μm.