Phases of Lung Development

Histology for Pathologist, 3rd Edition
Phase Gestation (approx. weeks) Major Events Embryonic 3 1/2–6 weeks Development of major airways Pseudoglandular 6–16 Development of airways to terminal bronchioles Canalicular 16–28 Development of the acinus and its vascularization Saccular 28–36 Subdivision of saccules by secondary crests Alveolar 36 weeks to term (and up to 4 years of age) Acquisition of alveoli

Table 18.3 Lung Development and Regulatory Factors*

Phase of Lung Development Events Major Molecular Mediators Embryonic Outgrowth of trachea, right and left main bronchi, and major airways HNF-3β, TTF-1, RA, RAR, Shh, Ptch, Gli2, Gli3, FGF-8, FGF-10, NHF-4, N-cadherin, activin-β-r, IIa, lefty-1/2, nodal, Pitx-2 Pseudoglandular Formation of bronchial tree up to a preacinar level. GATA-6, N-myc, PDGF, PDGF-R, EGF, EGF-R, FGF, TGF-β, Shh, Ptch, VEGF, BMP-4, RA, RAR Canalicular Formation of the pulmonary acinus and of the future air-blood barrier; increase of capillary bed; epithelial differentiation; first appearance of surfactant GATA-6, TTF-1, HNF-3β, Mash-1, VEGF Saccular Formation of transitory air spaces HNF-3β, TTF-1, NF1, VEGF, VEGF-R Alveolar Alveolarization by forming of secondary septa PDGF, PDGF-R, FGF, FGF-R, VEGF, VEGF-R, angiopoietins, ephrins, RA, RAR Microvascular maturation (birth–3 years) Thinning of interalveolar walls; fusion of the capillary bilayer to a single layered network VEGF, VEGF-R, PDGF, PDGF-R, angiopoietins, ephrins *Modified from: Roth-Kleiner M, Post M. Genetic control of lung development. Biol Neonate 2003;84:83–88.