The embryology of the normal esophagus and trachea is controversial. There are two main opinions regarding the role played by the tracheoesophageal (TE) septum. Similar controversy exists in explaining the embryology of anomalous TE development, mainly due to a lack of embryos demonstrating these anomalies at critical stages during development. Proposed theories can be divided into four main groups: intraembryonic pressure; epithelial occlusion; differential growth; and vascular occlusion. More recently, a new theory has been described based on analysis of anomalous TE development in adriamycin (doxorubicin)-exposed rat embryos. Impaired tracheal development, with the foregut developing into the trachea rather than the esophagus and associated with development of a dorsal pouch from the upper part of the foregut, gave rise to esophageal atresia with distal TE fistula. On the other hand, development of a ventral upper foregut pouch led to tracheal atresia. A laryngotracheo-esophageal cleft may result if no upper foregut pouches develop, with differentiation of the ventral half of the foregut into trachea and the dorsal half into esophagus. This review describes the basic theories of normal and abnormal TE development in mammalian embryos and presents new data related to this abnormality.
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