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There are five stages of human lung development: the embryonic period, occurring between 3 and 6 weeks of gestation; the pseudoglandular period, from 6-16 weeks of gestation; the canalicular period, from 16-28 weeks; the saccular period from 28-36 weeks; and the alveolar period, from 36 weeks of gestation to about 4 years of age (10). Fetal lung development begins with the formation of the primitive lung bud which arises from the foregut, and is first seen as a groove in the floor of the primitive pharynx evaginates into distinct laryngotracheal diverticulum and then elongates caudally into the primitive mesenchyme. The lung bud is lined with endodermally derived epithelium. Formation of the major airways occurs during the embryonic period through a dichotomous branching of the diverticulum (101).

Budding and branching of the airways continues through the pseudoglandular period and results in the formation of the small airways including the terminal bronchioles. Budding and branching occur in response to stimuli produced in the surrounding mesoderm. By 16 weeks of gestation the branching of conducting portion of the tracheobronchial tree is complete, resulting in a bilobed left lung and a trilobed right lung. At this time four of the eight bronchiolar epithelial cell types comprising the mature lung are recognizable: ciliated, non-ciliated (pre-Clara), secretory and early basal (37).

The respiratory structures and surrounding vasculature of the lung begin to develop during the canalicular phase. Capillaries are positioned in close proximity to the airway epithelium in order to allow future gas exchange. The primitive respiratory bronchioles arise from the terminal bronchioles and contain terminal sacs that will later give rise to alveoli.

Development of the alveoli begins in the saccular phase with the subdivision of saccules, terminal clusters of airways. These primitive alveoli are pouches in the walls of saccules and respiratory bronchioles and are lined by type I cells. Development of true vascularized alveoli occurs in the alveolar phase. These alveoli are lined by type I cells and also contain alveolar type II cells necessary for the production of surfactant. During the alveolar phase, secondary septa grow into the airspaces partitioning the more primitive pouches into alveolar ducts and sacs. When fully developed, the structure of the alveoli is analagous to a square room with one wall missing, where they open directly into respiratory bronchioles or alveolar ducts and sacs.

For additional information about lung development and cells of the pulmonary epithelium see:

An Overview of Lung Development
Respiratory Portion (pneumocytes)

Murine lung development begins at embryonic day 9 (E9) when the lung bud arises as an evagination from the primitive esophagus. Murine lung development has been divided into four chronological stages similar to the stages of human lung development. First is the pseudoglandular stage which lasts from E9.5-E16.6, during which the bronchial and respiratory tree develops, giving rise to a four lobed right lung and a one lobed left lung. During the canalicular stage (E16.6-E17.4) terminal sacs and vascularization develop. The terminal sac stage occurs from E17.4-P5 during which the number of terminal sacs and extent of vascularization increases and the alveolar type I and type II cells differentiate. Lung development is completed during the alveolar stage P5-P30 when the terminal sacs develop into mature alveolar ducts, sacs and alveoli (101).

The murine pulmonary epithelium is simpler than that of the human. The cell lineages of the airway epithelium are organized in a distinct proximal-distal pattern. The upper airways are lined with ciliated columnar cells and mucus secreting cells, while the lower airways are lined with Clara cells. The murine pulmonary epithelium is simpler than that of the human. The cell lineages of the airway epithelium are organized in a distinct proximal-distal pattern. The upper airways are lined with ciliated columnar cells and mucus secreting cells. The lower airways are lined mainly with Clara cells but also contain rare neuroendocrine cells.

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