{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:54:47Z","timestamp":1791287687476,"version":"4.1.0"},"reference-count":114,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-2\/"}],"funder":[{"name":"Deutsches Forschungszentrum f\u00fcr Gesundheit und Umwelt, Helmholtz Zentrum M\u00fcnchen","id":[{"id":"https:\/\/ror.org\/00cfam450","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Horizon 2020","award":["874839"],"award-info":[{"award-number":["874839"]}]},{"name":"Novo Nordisk","award":["NNF17CC0027852"],"award-info":[{"award-number":["NNF17CC0027852"]}],"id":[{"id":"https:\/\/ror.org\/0435rc536","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>During embryogenesis, morphologically diverse epithelial organs bud from different regions of the embryonic gut. The unique features of each nascent organ result from distinct cell fate specification and morphogenetic events elicited by organ-inducing cues. Retinoic acid is a powerful inducer of the pancreas, yet how it regulates pancreas specification and budding from the foregut endoderm remains poorly understood. By modeling these processes using a new human embryonic stem cell (hESC) organoid system, we demonstrate that both pancreas budding and specification are induced by RAR:RXR signaling. On the molecular level, we identify \u03b2-catenin as an important downstream target and propose that the reduction of \u03b2-catenin at the cell membrane weakens cell-cell adhesion (resulting in perturbed apical-basal cell polarity and gut epithelium multi-layering), while its nuclear depletion relieves \u03b2-catenin-mediated repression of FOXA2-dependent Pdx1 transcriptional activation. Our findings provide a new framework by which developmental cues coordinate both morphogenetic and cell specification events by targeting proteins with dual roles in cell-cell adhesion and transcription, such as \u03b2-catenin.<\/jats:p>","DOI":"10.1242\/dev.205876","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:23:54Z","timestamp":1789651434000},"source":"Crossref","is-referenced-by-count":0,"title":["Parallel regulation of tissue morphogenesis and cell-fate specification by RAR:RXR signaling during pancreas formation"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9033-1839","authenticated-orcid":false,"given":"Ivan","family":"Kulik","sequence":"first","affiliation":[{"name":"Institute of Translational Stem Cell Research (ITS), Helmholtz Center Munich 1 , Munich 85764,","place":["Germany"]},{"name":"Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen 2 , Copenhagen 2200,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5705-2851","authenticated-orcid":false,"given":"Chenglei","family":"Tian (\u7530\u6210\u78ca)","sequence":"additional","affiliation":[{"name":"Institute of Translational Stem Cell Research (ITS), Helmholtz Center Munich 1 , Munich 85764,","place":["Germany"]},{"name":"Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen 2 , Copenhagen 2200,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5842-2623","authenticated-orcid":false,"given":"Sabina","family":"Chubanava","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Obesity (IDO), Helmholtz Center Munich 3 , Munich 85764,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-5453","authenticated-orcid":false,"given":"Adrian","family":"Villalba","sequence":"additional","affiliation":[{"name":"Institut Cochin, CNRS, INSERM, Universit\u00e9 Paris Cit\u00e9 4 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-7367","authenticated-orcid":false,"given":"Natalie","family":"Krahmer","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Obesity (IDO), Helmholtz Center Munich 3 , Munich 85764,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-337X","authenticated-orcid":false,"given":"Raphael","family":"Scharfmann","sequence":"additional","affiliation":[{"name":"Institut Cochin, CNRS, INSERM, Universit\u00e9 Paris Cit\u00e9 4 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6747-787X","authenticated-orcid":false,"given":"Henrik","family":"Semb","sequence":"additional","affiliation":[{"name":"Institute of Translational Stem Cell Research (ITS), Helmholtz Center Munich 1 , Munich 85764,","place":["Germany"]},{"name":"Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen 2 , Copenhagen 2200,","place":["Denmark"]},{"name":"Lund University 5 Department of Clinical Sciences , , Malm\u00f6 20213,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"2026100607254422700_DEV205876C1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/385257a0","article-title":"Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells","volume":"385","author":"Ahlgren","year":"1997","journal-title":"Nature"},{"key":"2026100607254422700_DEV205876C2","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S0092-8674(04)00114-X","article-title":"Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD","volume":"116","author":"Baas","year":"2004","journal-title":"Cell"},{"key":"2026100607254422700_DEV205876C3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ydbio.2014.03.019","article-title":"Distinct requirements for beta-catenin in pancreatic epithelial growth and patterning","volume":"391","author":"Baumgartner","year":"2014","journal-title":"Dev. 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