Morphological studies of the developing human esophageal epithelium

Abstract

This article focusses on the structural development of human esophageal ciliated epithelium. A combination of transmission electron microscopic (TEM), scanning electron microscopic (SEM), radioautographic, and light microscopic (LM) analyses were carried out using intact fetal tissues between 8 and 20 weeks of gestation as well as cultured esophageal explants. Up to the age of 10 weeks, the stratified esophageal epithelium consisted of two longitudinal primary folds. The surface cells were undifferentiated and contained large glycogen aggregates. Between 11 and 16 weeks, the primary folds (now up to four) had developed secondary folds. The thickness of the epithelium drastically increased (123%) in concomittance with a differentiation of surface columnar ciliated cells. These highly specialized surface cells exhibited junctional complexes and well-developed organelles with numerous microvilli interspersed among the cilia. Transverse sections revealed the internal structure of the cilia with a consistent pattern of nine doublet microtubules surrounding a central pair of single microtubules. Freeze-fracture studies illustrated the presence of a ciliary necklace composed of 6 ring-like rows of intramembranous particles. They also revealed the structure of ciliary cell tight junctions consisting of up to nine anastomosing strands (P-face) or complementary grooves (E-face). Ultrastructural studies (LM, TEM, SEM) of the esophageal squamous epithelium obtained after 15 days of culture showed that the newly formed epithelium was similar to adult human epithelium. Finally LM and SEM observations established that the esophagogastric junction was not yet well delineated, consisting of a transitional area composed of a mixture of esophageal ciliated cells and gastric columnar mucous cells.

Pattern Selection in Growing Tubular Tissues

“…Our results are thus in excellent agreement with empirical observations: gastrointestinal embryonic tissues with a thicker outer layer, e.g., the esophagus with H en =H me ≃ 1.8=1.9 [36], fold circumferentially, while tissues with a thinner outer layer, e.g., the jejunum with H en =H me ≃ 1.1=1.4 [37], fold longitudinally like the valves of Kerckring. Our results are also in qualitative agreement with recent biological experiments on embryonic intestines: circumferential folding patterns emerge on the mucosal surface of chick embryos with μ en =μ me ≪ 1 where the mesoderm is highly stiffened by early muscle differentiation, while square folding patterns appear in mouse embryos where both layers have similar stiffnesses of μ en =μ me ≃ 1.5 [5].…”

Differentiated and functional human airway epithelium regeneration in tracheal xenografts

“…This result confirms the idea that the squamous epithelium phenotype represents a ''highly protective'' phenotype against injurious agents. This metamorphism is also observed in normal development when the columnar ciliated epithelium of the esophagus is transformed into squamous epithelium at 3-4 mo of human fetal life (26). With regard to the junctional complexes involved, it has been shown in models of airway injury that a rapid development of effective tight junctions is responsible for such a rapid restoration of epithelial barrier integrity (9,16,25).…”

Transcript Profiling Identifies Dynamic Gene Expression Patterns and an Important Role for Nrf2/Keap1 Pathway in the Developing Mouse Esophagus

“…The ciliated epithelium is then gradually replaced by a squamous epithelium until a non-keratinized stratified squamous epithelium. Morphological changes during human esophageal development have been well-characterized for several decades [2], [3]. However, the molecular mechanisms underlying these morphological changes remain largely unknown.…”