Developmental Changes in the Structure of the Rat Fetal Lung, with Special Reference to the Airway Smooth Muscle and Vasculature.

Abstract

Structural changes in the developing rat lung were studied by a combined use of light microscopy including immunohistochemistry for a-smooth muscle actin (alpha-SMA) and scanning electron microscopy (SEM) using the KOH-collagenase digestion method. In the embryonic stage (E11-E13), the lung bud appeared as an outgrowth from the ventral wall of the foregut which grew caudally into the splanchnic mesoderm to form a pair of bronchial buds at the end. At E13, the airway smooth muscle cells first appeared around the bifurcation of the trachea. These smooth muscle cells were restricted to the dorsal surface of the tracheal epithelium, suggesting a difference in character between the dorsal and ventral sides of the mesenchymal cells in this region. During the pseudoglandular stage (E13-E18.5), the bronchial buds repeatedly gave off branches in the mesenchymal tissue. The smooth muscle cells in the bronchioles were spindle-shaped and arranged completely circularly around the epithelial tube, except that the terminal bud of bronchioles lacked the smooth muscles. The neck of the terminal bud was constantly surrounded by flat and irregularly-shaped immature smooth muscle cells, representing an early event in the smooth muscle cell differentiation from mesenchymal cells. In the canalicular to saccular stages (E18.5 to birth), the terminals of bronchioles became saccular, thus forming prospective alveolar acini. At birth, the alveolar wall became thinner than before birth, and the individual smooth muscle cells in bronchioles were elongated like a tape. As to the blood vessel differentiation, various sized sinusoidal spaces indicating the primitive blood vessels were already present in the mesenchymal tissue at E11.5. The endothelial cells of these sinusoidal spaces were irregularly shaped and sometimes extended their processes into the lumen. The network of tubular vessels appeared from E14.5. These vessels had tapering ends as well as transluminal trabeculae, suggesting that capillary growth proceeds by both the sprouting and partitioning (i.e., intussusception) of vessels in the pseudoglandular stage.

Wnt signaling in lung organogenesis

“…Epithelial structures lining the arborized system are derived from the foregut endoderm while adjacent mesenchymal structures are derived primarily from the splanchic mesenchyme and first appear on the dorsal aspect of the trachea at the level of the first bifurcation. 5 Nervous tissue is present in the form of two large nerve trunks that parallel the airway tree 6 and are likely to be derived from the neural crest. The airway and alveolar epithelium exhibit specialized structural features that are specific to regulation of the epithelial barrier, host defense, immunomodulation, water/ ion balance, metabolism, detoxification and protection from physical stress.…”

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs

“…IUGR pups are 20 -25% lighter than the sham-operated control animals (controls), birth weights are normally distributed within and among litters, and litter size does not differ significantly between control and IUGR groups (51)(52)(53)(54)(55)(56)(57). Notably, at term birth, rat lungs are in the saccular stage of lung development, equivalent to a human fetus ranging from 24 to 36 wk of gestation (11,13,87).…”

Distribution of ERK1/2 and ERK3 during normal rat fetal lung development

“…To identify the cell types associated with the P-ERK1/2 signal, double label fluorescent immunohistochemistry on E17 fetal rat lung tissue sections was used with the following cell-specific marker antibodies including: thyroid transcription factor I (Titf1) and hepatocyte nuclear factor 3-b (Foxa2) for immature epithelial cells; T1a, for type I epithelial cells; plateletendothelial cell adhesion molecule 1 (PECAM1) for endothelial cells; and a-smooth muscle actin for smooth muscle cells (Marszalek et al 2000;Ramirez et al 2003;Yamada et al 2002;Zhou et al 1996). Figure 3c shows that P-ERK1/2 staining colocalized with all marker antibodies, suggesting that P-ERK1/2 is not limited to a specific cell type in the fetal rat lung at E17.…”

“…To determine which epithelial cell types are associated with ERK3 expression, double label fluorescent immunohistochemistry on E17 and E21 fetal rat lungs were carried out with the following cell-specific antibodies: Titf1 and Foxa2 for immature epithelial cells, surfactant proteins B (SpB) and C (SpC), for type II epithelial cells, T1a, for type I epithelial cells, PECAM1 for endothelial cells, and a-smooth muscle actin for smooth muscle cells (Marszalek et al 2000;Ramirez et al 2003;Yamada et al 2002;Zhou et al 1996). Figure 5b shows that ERK3 staining colocalizes with Titf1, Foxa2, and T1a at E17, confirming that ERK3 is epithelial specific.…”