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As it develops, the esophageal lining is transformed from a simple columnar epithelium into a stratified squamous cell layer, accompanied by the replacement of unspecified mesenchyme with layers of muscle cells. Studies in animal models have provided significant insights into the roles of various signaling pathways in esophageal development. More recent studies using human pluripotent stem cells (hPSCs) further demonstrate that some of these signaling pathways are conserved in human esophageal development. In addition, a combination of mouse genetics and hPSC differentiation approaches have uncovered new players that control esophageal morphogenesis. In this Review, we summarize these new findings and discuss how the esophagus is established and matures throughout different stages, including its initial specification, respiratory-esophageal separation, epithelial morphogenesis and maintenance. We also discuss esophageal muscular development and enteric nervous system innervation, which are essential for esophageal structure and function.<\/jats:p>","DOI":"10.1242\/dev.193839","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T12:50:13Z","timestamp":1617022213000},"source":"Crossref","is-referenced-by-count":62,"title":["The development and stem cells of the esophagus"],"prefix":"10.1242","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-0750","authenticated-orcid":false,"given":"Yongchun","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-6701","authenticated-orcid":false,"given":"Dominique","family":"Bailey","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Que","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"2021042701194506200_DEV193839C1","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1242\/dev.007674","article-title":"SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation","volume":"134","author":"Ai","year":"2007","journal-title":"Development"},{"key":"2021042701194506200_DEV193839C2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/ncb2963","article-title":"Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change","volume":"16","author":"Alcolea","year":"2014","journal-title":"Nat. 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