Talk:SH Lecture - Respiratory System Development

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Lung Development Stages

Text from: <pubmed>10852845</pubmed>| PMC1637815 | Environ Health Perspect.

Embryogenesis

The lungs in humans first appear at the end of the first month of gestation as an evagination of epithelium from the foregut. The bud rapidly divides as a series of branching tubes in a dichotomous pattern. These tubular branches invade and interdigitate with mesenchymal tissues. Branching morphogenesis during this period forms the most proximal portions of the future tracheobronchial tree. As these tissues grow, they push into the future pleuroperitoneal cavity of the embryo. During embryogenesis, transcription factors play an important role in gene expression and regulation. Transcription factors are essential in both the stimulation and inhibition of gene expression to regulate the proper temporal and spatial patterning of lung development. Hepatocyte nuclear factor- 3 (12) and the homeobox gene TTF-1 (13) are examples of transcription factors serving as important regulators of early differentiation of the pulmonary epithelium during this period. Lung development is also highly dependent on interactions between the epithelium and mesenchyme. This dual origin of lung tissues is critical in development. Removal of mesenchyme from the tip of a lung bud during early phases of development with transplantation to the side of a higher ordered segment abolishes further branching at the site of removal while stimulating growth of a

Pseudoglandular stage.

Tubular branching of the human lung airways continues from the fifth to the seventeenth week of gestation. As early as 2 months of gestational age, all segmental bronchi are present. During this period, the lungs take on the appearance of a glandlike structure. This stage is the most critical for the formation of all conducting airways. During this period, the airway tubular structures are lined with tall columnar epithelium, whereas the more distal structures are lined with cuboidal epithelium. A number of signals arising from epithelial mesenchymal interactions during this time continue to modulate cellular proliferation temporally as well as spatially (4). These regulatory signals lead to further branching morphogenesis by affecting the rate of cellular proliferation (15). The presence of extracellular matrix molecules, including collagen, fibronectin, laminin, glycosaminoglycans, and proteoglycans, as well as cell membrane-bound integrins, also plays an important role in directing lung development by influencing the rates of cellular proliferation and differentiation (3,16,1/). Mechanical distention exerted on the lung as well as on specific cell types can also significantly affect gene expression and, ultimately, lung growth and development (4). A variety of growth factors and growth factor receptors are also important in controlling cellular functions (3). Epidermal growth factor, transforming growth factor-a, and retinoic acid all act to affect branching morphogenesis and cellular differentiation (18,19). Epithelial differentiation of ciliated, goblet, and basal cells first appears in the most central airways during this stage of development. Cartilage and smooth muscle cells are also first noted in the trachea and extend more peripherally with progressive growth of the lungs. During this stage of

Canalicular stage.

This stage lasts from week 16 to week 24 in the human fetus. Lung morphology changes dramatically during this time because of differentiation of the pulmonary epithelium, resulting in the formation of the future air-blood tissue barrier. Surfactant synthesis and the canalization of the lung parenchyma by capillaries begin. During this stage, the future gas exchange regions can be easily distinguished from the future conducting airways of the lungs.

Saccular stage.

The saccular stage of lung development in humans lasts from week 24 to near term. The most peripheral airways form widened airspaces, termed saccules. These saccules widen and lengthen the airspace, in large measure by the addition of new generations. During this stage, the future gas exchange region expands significantly. Populations of fibroblastic cells also undergo differentiation during this stage. These fibroblast-like cells are responsible for the production of the extracellular matrix, collagen, and elastin. It is also presumed that they play an important role in epithelial differentiation and control of surfactant secretion in connection with the growth of the gas exchange region during this stage. The vascular tree also grows in length and diameter during this time.

Columnar cells that are undifferentiated characterize the first epithelial cells lining fetal lung tubules. The first epithelial cells to differentiate in the trachea are neuroendocrine cells, followed closely by ciliated cells, and finally basal and secretory cells in rapid sequence. This process of differentiation covers a developmental period ranging from days to months. In rodents including the mouse, rat, and hamster, complete epithelial differentiation of the trachea occurs in as little as 2 days. In primate trachea, cellular differentiation takes up to 6 months to be complete. In most species, epithelial cell differentiation of the trachea usually is not complete until just before birth. For more peripheral airway generations, cellular differentiation is likely to continue into the early postnatal period. Fetal epithelial cells are typically filled with glycogen that is gradually replaced with a granular cytoplasm filled with numerous organelles during cellular differentiation. These glycogen-filled cells are found throughout the tracheobronchial tree as well as into the most peripheral saccules. Differentiation of the epithelium is highly site specific, giving rise to more than 10 different cell types. For example, within the saccules of the lungs, cells lining these surfaces differentiate to form both squamous type 1 cells as well as cuboidal type 2 cells. The presence of glycogen within these cells may persist into early postnatal life.

Talk:SH Lecture - Respiratory System Development

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Lung Development Stages