ABSTRACT
The lung is designed to provide a large gas exchange surface area where capillary blood very efficiently comes into close contact to the inspired air. This goal is achieved by a sequence of different developmental processes. Organogenesis starts with a ventral outpouching of the foregut resulting in the appearance of the lung buds (for the timing of lung development in different species see Table 1). The following development of the airways and the gas exchange area requires two quite different steps. First, the conducting and parts of the respiratory airways are formed by continuous cycles of branching and grow into the surroundingmesenchyme starting at the lung buds (branching morphogenesis). Most of this development takes place during the pseudoglandular stage. Second, during the alveolar stage the distal part of the bronchial tree is further enlarged by a lifting off of new, secondary septa from existing primary septa (septation/alveolarization). The canalicular and saccular stages may be considered as intermediate stages, occurring between pseudoglandular and alveolar stage. Very important, during the canalicular stage the first functional gas exchange surface (air-blood barrier) is formed. During the saccular stage the switch from branching to septation occurs. In
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Table 1 Stages and Duration of Lung Development
Period Stage Duration Characteristics
Embryonic Embryonic Rabbit: n.d.–E18
Sheep: E17-E30 Human: E26-E49 (4-7 weeks)
Mouse: E9.5-E12 Rat: E11-E13
Start of organogenesis;
formation of major airways
Fetal Pseudoglandular Rabbit: E18-E24 Sheep: E30-E85
Human: E35-E119 (5-17 weeks)
Mouse: E12-E16.5
Rat:E13-E18.5
Formation of bronchial tree and
large parts of prospective respiratory
parenchyma; birth of the acinus
Canalicular Rabbit: E23-E27
Sheep: E80-E120 Human: E112-E182 (16-26 weeks)
Mouse: E16.5-E17.5 Rat: E18.5-E20
Completion of
conducting airways; epithelial differentiation; first
air-blood barrier; appearance of surfactant
Saccular or
terminal sac
Rabbit: E27-E30
Sheep: E110-E140
Expansion of air
spaces Human: E168-E266 (24 weeks-term)
Mouse: E17.5-P4 Rat: E21-P4
Alveolar Rabbit: E30-term
(E31) Sheep: E120-term (E145)
Alveolarization by
formation of secondary septa (septation)
Postnatal Human: E252 (36 weeks preterm)-1-2 years
Mouse: P4-P14
Rat: P4-P14 Microvascular maturation
Rabbit: unknown Sheep: unknown
Human: 0-3 years Mouse: P14-P21 Rat: P14-P21
Remodeling and maturation of
interalveolar septa and of the capillary bed
Normal Growth Rabbit: Birthadulthood
normal growth of the lungs
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order to optimize gas exchange after bulk alveolarization is completed, the interalveolar septa and their capillary networks are remodeled during the phase of microvascular maturation. At this point lung development is viewed as finished and normal growth of the organ follows. Relative to lung development, the time point of birth differs between mammals. In humans, birth happens at the beginning of the alveolar stage.
