Tracheal morphogenesis and fetal development of the mucociliary epithelium of the rat

In the rat, tracheal development begins at mid-gestation (Day 11) with the formation of the tracheal groove, a longitudinal diverticulum of endodermal epithelium that evaginates from the floor of the pharynx and tubular foregut. At this stage the tracheal groove and developing foregut share a common lumen. Paired primary bronchial buds (lung buds), surrounded by lung bud mesenchyme (splanchnic mesoderm), arise from the caudal end of the tracheal groove. The formation of a longitudinal tracheoesophageal septum divides the combined tracheal groove and developing foregut into two structures, the trachea and esophagus. The trachea and esophagus grow apart, surrounded by independently organized populations of mesenchymal cells. Near this time (Day 12-13), the primary bronchial buds give rise to secondary (lobar) buds of pulmonary epithelium. This establishes the lobar pattern of the right and left lungs and marks the formation of extrapulmonary bronchi. The development of smooth muscle and cartilage within the tracheal mesenchyme precedes the differentiation of the mucociliary epithelium. Smooth muscle forms transversely oriented fascicles in the dorsal tracheal wall (pars membranacea), while pre-cartilage rings surround the remaining ventral and lateral walls (pars cartilagina). Epithelial differentiation is first evident at Day 17, with the formation of ciliated cells in the epithelium of the pars membranacea. Differentiation in the pars cartilagina trails development in the dorsal epithelium. Cell surface characteristics of the tracheal epithelium indicate that secretory cells differentiate about Day 19-20. The precise time and sequence of differentiation of mature cell types of the tracheal epithelium is yet to be determined. It is clear, however, that the development of the mucociliary epithelium in the rat is not completed at birth, but continues into the neonatal period.