Chapter category: Development
Lung Epithelial Morphogenesis: Integrated Functions of Transcriptional Factors, Peptide Growth Factors, Extracellular Matrix, Physiological and Environmental Factors
Molecular Basis of Epithelial Appendage Morphogenesis
Edited by: Cheng-Ming ChuongISBN: 1-57059-490-2
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Chapter authors:
David Warburton, Guillermo Flores-Delgado, Ding Bu, Kathryn D. Anderson and Richard E. Olver
The mammalian lung has the largest surface area of any epithelial appendage in the hu-man body. Its intricate vaulted structure could indeed be considered a veritable "biological cathedral". The lung develops as an epithelial appendage of the primitive foregut in the early embryo, undergoes extensive branching morphogenesis in utero and continues to undergo alveolarization and increases in surface area postnatally. The human lung achieves a final gas diffusion surface area of 70 m2 by 0.1mm thick in young adulthood. This is an area about 40 times the surface area of the next largest epidermal appendage, the skin. It is capable of supporting a systemic oxygen consumption ranging between 250 ml/min at rest to 5500 ml/min during exercise. A matching capillary network also develops in close apposition to the alveolar surface which can accommodate a blood flow rising from 4 to 40L/min during the transition from rest to maximal exercise.1
The lung originates as a ventral appendage of the endodermal epithelium lining the floor of the primitive embryonic anterior pharynx at E9.5 days in the mouse (Fig.12.1). It then divides laterally into two buds and begins dichotomous branching into the surrounding splanchnic mesenchyme. This repetitive epithelial branching process, termed branching morphogenesis, is characteristic of lung formation and continues throughout gestation. Histologically, lung development has been divided into four chronological stages in the mouse:
- pseudoglandular stage (E9.5-E16.6), during which the bronchial and respiratory tree develops and an undifferentiated primordial system forms;
- canalicular (E16.6-E17.4)terminal sacs and vascularization develop in this period;
- terminal sac stage (E17.4-postnatal day 5 (P5))number of terminal sacs and vascularization increase and type I and II cells differentiate; and
- alveolar stage (P5-P30)terminal sacs develop into mature alveolar ducts and alveoli
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