Morphogenesis of the Mammalian Lung: Aspects of Structure and Extracellular Matrix

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. InMD: MASSARO, JOB: 03313, PAGE:MD: MASSARO, JOB: 03313, PAGE:Table 1 Stages and Duration of Lung DevelopmentPeriod Stage Duration CharacteristicsEmbryonic Embryonic Rabbit: n.d.–E18Sheep: E17-E30 Human: E26-E49 (4-7 weeks)Mouse: E9.5-E12 Rat: E11-E13Start of organogenesis;formation of major airwaysFetal Pseudoglandular Rabbit: E18-E24 Sheep: E30-E85Human: E35-E119 (5-17 weeks)Mouse: E12-E16.5Rat:E13-E18.5Formation of bronchial tree andlarge parts of prospective respiratoryparenchyma; birth of the acinusCanalicular Rabbit: E23-E27Sheep: E80-E120 Human: E112-E182 (16-26 weeks)Mouse: E16.5-E17.5 Rat: E18.5-E20Completion ofconducting airways; epithelial differentiation; firstair-blood barrier; appearance of surfactantSaccular orterminal sacRabbit: E27-E30Sheep: E110-E140Expansion of airspaces Human: E168-E266 (24 weeks-term)Mouse: E17.5-P4 Rat: E21-P4Alveolar Rabbit: E30-term(E31) Sheep: E120-term (E145)Alveolarization byformation of secondary septa (septation)Postnatal Human: E252 (36 weeks preterm)-1-2 yearsMouse: P4-P14Rat: P4-P14 Microvascular maturationRabbit: unknown Sheep: unknownHuman: 0-3 years Mouse: P14-P21 Rat: P14-P21Remodeling and maturation ofinteralveolar septa and of the capillary bedNormal Growth Rabbit: Birthadulthoodnormal growth of the lungsMD: MASSARO, JOB: 03313, PAGE: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.