Figure 7.

Characterization of type I AECs differentiation. The normal distal saccules of wild-type (+/+) at near term (E20.5) showed typical type I (t1) and type II (t2) epithelial cells (panel A, arrowheads), but knockout (-/-) littermate lungs showed less developed saccules lined by columnar epithelial cells (panel B, black arrowheads), with partially arrested tubules in the distal lung (panel B, green arrowheads). Immunostaining for type I cell markers T1α and AQP5 demonstrated an intense staining in flat epithelial cells in wild-type lungs at E20.5 (panels C and E, arrowheads). In contrast, in knockout littermate lungs, T1α and AQP5 staining was dramatically decreased (panels D and F, arrowheads). Megalin expression (Meg) was detected in the airway epithelial cells, but not in proximal bronchiole epithelial cells (data not shown) in the lungs from both wild-type and knockout at E20.5. The elongated megalin-positive epithelial cells, lining the normally developed sacculi, were readily evident in many areas of the wild-type lungs. In contrast, the terminal epithelial cells positively stained by megalin antibodies in knockout lungs were comprised mainly of undifferentiated cuboidal cells (compare the arrowheads in G and H). Original magnification: A, B, G and H are 60X, C-F are 40X.