{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:29:47Z","timestamp":1772591387116,"version":"3.50.1"},"reference-count":25,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP19K16184"],"award-info":[{"award-number":["JP19K16184"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions.<\/jats:p>","DOI":"10.1242\/bio.048728","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T09:34:17Z","timestamp":1580117657000},"source":"Crossref","is-referenced-by-count":22,"title":["The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components"],"prefix":"10.1242","author":[{"given":"Machiko","family":"Teramoto","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences and Institutes for Protein Dynamics and Comprehensive Research, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Institutes for Protein Dynamics and Comprehensive Research, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsura","family":"Minegishi","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Uchikawa","sequence":"additional","affiliation":[{"name":"Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kuroiwa","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Ishii","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Institutes for Protein Dynamics and Comprehensive Research, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan"},{"name":"Department of Biology, School of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-7014","authenticated-orcid":false,"given":"Hisato","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Institutes for Protein Dynamics and Comprehensive Research, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042622421334300_BIO048728C1","doi-asserted-by":"publisher","first-page":"e1002866","DOI":"10.1371\/journal.pgen.1002866","article-title":"Multiple roles and interactions of Tbx4 and Tbx5 in development of the respiratory system","volume":"8","author":"Arora","year":"2012","journal-title":"PLoS Genet."},{"key":"2021042622421334300_BIO048728C2","doi-asserted-by":"publisher","first-page":"e5845","DOI":"10.1371\/journal.pone.0005845","article-title":"Retinoic acid signaling organizes endodermal organ specification along the entire antero-posterior axis","volume":"4","author":"Bayha","year":"2009","journal-title":"PLoS ONE"},{"key":"2021042622421334300_BIO048728C3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1242\/dev.027045","article-title":"The engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum","volume":"137","author":"Cheng","year":"2010","journal-title":"Development"},{"key":"2021042622421334300_BIO048728C4","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1242\/dev.053694","article-title":"Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2","volume":"138","author":"Domyan","year":"2011","journal-title":"Development"},{"key":"2021042622421334300_BIO048728C5","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.devcel.2009.02.010","article-title":"Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2","volume":"16","author":"Gao","year":"2009","journal-title":"Dev. 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