Figure 3

Histological analysis of wild-type and Ptdsr ^-/-organs during embryogenesis. (a-f) Wild-type embryos and (g-l) Ptdsr ^-/- littermates were isolated at various embryonic stages, serially sectioned sagittally and analyzed for developmental abnormalities in detail after H&E staining. At E16.5, the lungs of (g) Ptdsr ^-/- embryos had sacculation just starting, and well-formed alveoli (asterisks) or epithelium-lined bronchioles (arrows) were scarce compared to (a) wild-type lungs. At E16.5, the glomeruli (arrows) in the kidney of (h) Ptdsr ^-/- embryos were underdeveloped compared to (b) wild-type, collecting tubules (arrowheads) were missing and undifferentiated blastemas (asterisks) were more abundant. The jejunum had no intramural ganglia in Ptdsr ^-/-embryos (i; and arrows in c); and a well-developed submucosa (asterisk in c) was missing. Brain sections at E18.5 show that (j) Ptdsr ^-/-embryos may have herniation (arrow) of the hypothalamus through the ventral skull (secondary palate), most likely through Rathke's pouch, and a severe malformation of the cortex (asterisks) compared to (d) wild-type embryos. At E18.5, (e) wild-type and (k) Ptdsr ^-/- lungs showed normal sacculation and formation of alveoli (asterisks) and bronchioles (arrow). (f) Wild-type neonatal liver had significant numbers of megakaryocytes (arrows), compared to (l) homozygous mutant littermates, and higher numbers of erythropoietic islands and of mature erythrocytes. Hepatocellular vacuoles are due to glycogen stores (asterisks) that were not metabolized in perinatally dying Ptdsr ^-/- animals, in contrast to wild-type newborns. Scale bar, 100 μm, except for (d) and (j), 1 mm.