Esophageal development and epithelial homeostasis

Abstract

Rosekrans SL, Baan B, Muncan V, van den Brink GR. Esophageal development and epithelial homeostasis. Am J Physiol Gastrointest Liver Physiol 309: G216 -G228, 2015. First published July 2, 2015; doi:10.1152/ajpgi.00088.2015.-The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus. esophagus; development; homeostasis; stem cell; endoderm THE WORD ESOPHAGUS IS DERIVED from the Greek words ε (oisein, to carry) and ␣␥ε (phagein, to eat). This description fits well with the functional role of the esophagus that mainly serves to "carry food" into the stomach. From the pharyngoesophageal junction, the esophagus passes through the mediastinum and diaphragm and connects to the cardia of the stomach at the gastroesophageal junction or Z-line. The pharyngoesophageal and gastroesophageal junctions anatomically overlap with the upper and lower esophageal sphincters. Both sphincters are closed except during swallowing to assure a unidirectional flow of esophageal content toward the stomach and to prevent reflux of gastric content into the esophagus. The relatively simple histology of the esophageal epithelium corresponds with the fact that the esophagus has no role other than to pass food through the thorax to the stomach. It does not play a known digestive, endocrine, or metabolic role and the epithelium consists of a simple stratified squamous epithelium, which provides a good protective layer against the unmodified food stream on its way to the stomach. Despite the perhaps somewhat prosaic functional role of the esophagus compared with other organs in the body, we feel that it is essential to gain a better understanding of the mechanisms that regulate normal esophageal homeo...

The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another

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LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

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