Figure 3

Histological analyses of lungs at various embryonic stages. Panel A indicates lung sections stained with H and E, and taken at various gestational stages as indicated. The first two columns are at lower magnification (10X) and the last two columns at higher magnification (40X). The first and third columns are representative sections from wild-type (+/+) embryos and the second and fourth columns from knockout (-/-) embryos. No differences were visible at E14.5 or E16.5 (panel A, a-h). Significant differences were visible from E17.5 onwards (panel A, i-x). Distal tubules showed dilation and mesenchyme thinning, with progression of septation in wild-type lungs (panel A, i, m and q), whereas the knockout lungs showed less saccular structures and more mesenchyme (panel A, j, n and r). At higher magnifications of wild-type lungs (panel A, k, o and s), developing pre-alveoli and thinning mesenchyme (arrowheads) were seen but sections from knockout embryos showed a delay in this sequence of development (panel A, l, p and t). At birth, lungs from knockout pups showed deficient septation and thick-walled mesenchyme (panel A, x, arrowheads). Labels: de, distal epithelium; m, mesenchyme; PA, pulmonary artery; a, pre-alveoli; b, bronchi. Panel B shows the morphometric analyses of lung terminal sac spaces in lungs at various gestational stages. A significant reduction in the terminal sac space was noted from E17.5 onwards. Results are expressed as mean ± s.d.