Stages of normal tracheo-bronchial development in rat embryos: Resolution of a controversy

The embryonic events surrounding tracheo-esophageal separation remain contr oversial. The present study was undertaken to clarify early tracheo-bronchi al development in the rat embryo at a critical period of organogenesis. Twe nty-seven timed-mated Sprague-Dawley rats were divided into nine groups of three rats. Their embryos were harvested on gestational days 11-15 at inter vals of 8 h, processed and sectioned transversely. The sections were staine d with hematoxylin and eosin and examined serially. The foregut is a single tube on gestational day 11. During the following 16 h, there is localized and rapid growth of the respiratory epithelium and a laterocaudal expansion to form the bronchial buds and a protuberance on the ventral wall of the f oregut (future tracheal carina). From gestational days 12-12 + 8, cellular debris and apoptotic epithelial cells are specifically located in the trach eo-esophageal groove, resulting in collapse and fusion of the lateral walls of the foregut, effectively separating the trachea and esophagus. Afterwar ds, the epithelial proliferation dominates the process of tracheo-esophagea l separation until it reaches the caudal end of the laryngeal epithelial la mina on gestational day 15. The present study shows that separation of the trachea from the esophagus involves three consecutive stages: (i) epithelia l proliferation resulting in the formation of bronchial buds and the trache al carina; (ii) epithelial apoptosis leading to separation of the trachea a nd esophagus; and (iii) epithelial proliferation to complete the separation process.