ABSTRACT
The mammalian respiratory system is a complex organ comprising two partsthe trachea and the lung-which both develop from the foregut. The respiratory system has arisen relatively late in vertebrate evolution, and its primary function is gas exchange, a function critical to survival of the organism. The biological process and genetic pathways that influence lung development begin long before the lung buds form as ventral outpouching of the foregut. At embryonic day 6 (E6), just prior to onset of gastrulation, the embryonic portion of the developing embryo is composed of two epithelial layers-the epiblast, which forms the entire embryo, and the visceral endoderm (or hypoblast), which is replaced by definitive gut endoderm during gastrulation and eventually contributes only to the extraembryonic yolk sac [1,2]. Gastrulation begins at E6.5 with the formation of the primitive streak, with epiblast cells on one side undergoing an epithelial-mesenchymal transformation to generate mesoderm. With the formation of the primitive streak on the posterior side of the embryo, the anteroposterior (AP) axis of the embryo becomes morphologically obvious. Over the ensuing 24 h, the streak elongates and moves along the rim of the egg cylinder toward its distal tip. It is here, at the anterior end of the primitive streak, that a specialized structure known
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as the node forms. The node generates axial mesendoderm, which includes the mesoderm that contributes to the prechordal plate and notochord as well as the definitive gut endoderm. The posterior end of the primitive streak gives rise to extraembryonic mesoderm, and the lateral plate and paraxial mesoderm arise from the intervening regions of the streak. The definitive endoderm moves anteriorly, replacing the anterior visceral endoderm (AVE) and eventually gives rise to the endoderm of the foregut and midgut. The foregut begins as a ventral folding of endodermal tissue at the anterior end of the embryo. As the foregut begins to close off, several tissue buds begin to form and later become crucial parenchymal organs such as the thyroid, thymus, lung, liver, and pancreas. Therefore, proper formation of the foregut is a crucial step in lung development. Interestingly, relatively little is known about endodermal development compared to the knowledge that has accumulated regarding the mechanisms involved in mesodermal and ectodermal formation.
