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Lung  - Development and Stem Cells


Anatomical Structure and Function of the Lung:

The lungs are part of the respiratory system and are responsible for gas exchange. The endoderm and mesoderm contribute to lung development; the endoderm lining the respiratory diverticulum gives rise to the epithelium and glands of the tracheabronchi, and alveoli as well as the epithelial lining of the larynx, while the splanchnic mesoderm gives rise to the connective tissue, cartilageairway and vascular smooth muscles of the lungs.

Embryonic Development of the Lung:

Development of the lungs in the mouse embryo is a complex, multistage morphogenetic process which begins on E9, upon initiation of the respiratory diverticulum or lung buds from the ventral foregut endoderm. Development continues throughout the early postnatal stages. There are five phases of structural lung development that occur at progressive times during gestation, the timing indicated below is approximate, with variation between fetuses. Some controversy exists regarding the exact timing of each phase.

The first stage is called the embryonic stage (mouse E9-12, human 3-7 weeks), and is characterized by organogenesis. At this stage, the lung buds appear and mesenchyme-driven branching is evident.

In the pseudoglandular stage (mouse E12–15, human 5-17 weeks), all of the conducting airways are formed. In humans, 20 generations of branching are completed by week 16. Airway branching reaches the level of the acinus, which is a collective term for the respiratory zone of the lung. It contains the respiratory bronchiole, which by definition contains no cartilage in the wall, the alveolar ducts and the alveolar sacs. In addition, proximal-to-distal cellular differentiation of the conducting airways begins during this stage.

The following canalicular stage (mouse E15–17, human 16-26 weeks) is characterized by completion of the airway branching pattern, whereby extensive branching of the distal epithelium and mesenchyme results in formation of terminal sacs lined with epithelial cells. The interaction of these cells with the mesoderm-derived vasculature marks the early stages of the future gas-exchange region. Additional changes during this period include the development of bronchioli, decrease in interstitial tissue volume and differentiation of the cuboidal epithelium into type I and type II alveolar epithelial cells which signal the start of surfactant production.

The saccular or terminal sac stage (mouse E17 to PD5, human 26-36 weeks) is characterized by coordinated growth of the pulmonary parenchyma, thinning of the connective tissue between the airspaces, and further maturation of the surfactant system. This stage culminates in terminal sac formation and vasculogenesis, in conjunction with differentiation of alveolar epithelial cells (AEC) type I (main sites of gaseous exchange) and type II surfactant-producing cells. At birth, the functional lung is still structurally immature, since the alveoli, the gas-exchange units of the adult lung, are virtually non-existent.

In the alveolar or postnatal stage (mouse PD5 to PD30, human 36 weeks to postnatal 2 years), the terminal respiratory sacs mature into the functioning alveoli, which are connected to alveolar ducts. Alveoli lined with AEC Type I, and in intimate contact to pulmonary capillaries, contain surfactant produced by AEC Type II cells and have pores connecting them to adjacent alveoli.