By M. Demerec (Ed.)

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1007/978-3-319-21082-7_3 25 26 B. C. Yoder Normal Lung Development in Brief The classical stages of lung development: Lung development is classically subdivided into five overlapping stages in human and rodents, on the basis of gross histological features. The first four stages, termed the embryonic, pseudoglandular, canalicular, and saccular stages, occur during gestation. At the end of the saccular stage at about 36 weeks, lungs have formed alveolar ducts and air sacs. Alveolarization, the final stage of lung development, begins in the nearterm lung prior to birth but primarily occurs postnatally, during the first 2–3 years of life, and may continue at a slower rate beyond childhood [2, 3].

Unbekandt M, del Moral PM, Sala FG, Bellusci S, Warburton D, Fleury V (2008) Tracheal occlusion increases the rate of epithelial branching of embryonic mouse lung via the FGF10FGFR2b-Sprouty2 pathway. Mech Dev 125(3–4):314–324 13. Jesudason EC, Keshet E, Warburton D (2010) Entrained pulmonary clocks: epithelium and vasculature keeping pace. Am J Physiol Lung Cell Mol Physiol 299(4):L453–L454 14. Wuenschell CW, Sunday ME, Singh G, Minoo P, Slavkin HC, Warburton D (1996) Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages.

Perturbation of nitric oxide (NO) is associated with arrested alveolar and lung vascular growth: While the role of the endothelium-derived relaxing factor NO in the regulation of the pulmonary vascular tone in the perinatal period is well established [31], little was known about its potential role in the structural development of the pulmonary vasculature. Studies suggest that VEGF-induced lung angiogenesis is in part mediated by NO. SU5416 (VEGF inhibitor)-induced arrested alveolar and vascular growth in newborn rats is associated with decreased lung eNOS protein expression and NO production; treatment with inhaled NO improves vascular and alveolar growth in this model [32].

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