{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:48:54Z","timestamp":1790106534829,"version":"4.0.1"},"reference-count":65,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 CA272903"],"award-info":[{"award-number":["R01 CA272903"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UH3 DK119982"],"award-info":[{"award-number":["UH3 DK119982"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P01 HD093363"],"award-info":[{"award-number":["P01 HD093363"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shipley Foundation"},{"DOI":"10.13039\/100008796","name":"Allen Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008796","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The gastrointestinal (GI) tract is complex and consists of multiple organs with unique functions. Rare gene variants can cause congenital malformations of the human GI tract, although the molecular basis of these has been poorly studied. We identified a patient with compound-heterozygous variants in RFX6 presenting with duodenal malrotation and atresia, implicating RFX6 in development of the proximal intestine. To identify how mutations in RFX6 impact intestinal patterning and function, we derived induced pluripotent stem cells from this patient to generate human intestinal organoids (HIOs). We identified that the duodenal HIOs and human tissues had mixed regional identity, with gastric and ileal features. CRISPR-mediated correction of RFX6 restored duodenal identity. We then used gain- and loss-of-function and transcriptomic approaches in HIOs and Xenopus embryos to identify that PDX1 is a downstream transcriptional target of RFX6 required for duodenal development. However, RFX6 had additional PDX1-independent transcriptional targets involving multiple components of signaling pathways that are required for establishing early regional identity in the GI tract. In summary, we have identified RFX6 as a key regulator in intestinal patterning that acts by regulating transcriptional and signaling pathways.<\/jats:p>","DOI":"10.1242\/dev.202529","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:55:15Z","timestamp":1712573715000},"source":"Crossref","is-referenced-by-count":10,"title":["RFX6 regulates human intestinal patterning and function upstream of PDX1"],"prefix":"10.1242","volume":"151","author":[{"given":"J. Guillermo","family":"Sanchez","sequence":"first","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Rankin","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Paul","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"},{"name":"University of North Carolina at Chapel Hill School of Medicine 3 Department of Cell Biology and Physiology , , Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Kechele","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5858-6759","authenticated-orcid":false,"given":"Jacob R.","family":"Enriquez","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana-Hawa","family":"Jones","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center 4 Division of Endocrinology , , Cincinnati, OH 45229 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri A. W.","family":"Greeley","sequence":"additional","affiliation":[{"name":"University of Chicago 5 Department of Medicine , , Chicago, IL 60637 , USA"},{"name":"University of Chicago 6 Department of Pediatrics , , Chicago, IL 60637 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Letourneau-Freiberg","sequence":"additional","affiliation":[{"name":"University of Chicago 5 Department of Medicine , , Chicago, IL 60637 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Zorn","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansa","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center 4 Division of Endocrinology , , Cincinnati, OH 45229 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4218-128X","authenticated-orcid":false,"given":"James M.","family":"Wells","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 1 Division of Developmental Biology , , USA"},{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229 2 , USA"},{"name":"Cincinnati Children's Hospital Medical Center 4 Division of Endocrinology , , Cincinnati, OH 45229 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"2024092011162329200_DEV202529C1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1471-2164-6-69","article-title":"Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes","volume":"6","author":"Anderle","year":"2005","journal-title":"BMC Genomics"},{"key":"2024092011162329200_DEV202529C2","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"2024092011162329200_DEV202529C3","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.ydbio.2006.07.020","article-title":"Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression","volume":"298","author":"Boyer","year":"2006","journal-title":"Dev. 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