{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:56:05Z","timestamp":1790639765390,"version":"4.1.0"},"reference-count":93,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SCHM 855\/4-1"],"award-info":[{"award-number":["SCHM 855\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["KO 6390\/1-1"],"award-info":[{"award-number":["KO 6390\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Seventh Framework Programme"},{"name":"Helmholtz Association"},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Although the role of the transcription factor NF-\u03baB in intestinal inflammation and tumor formation has been investigated extensively, a physiological function of NF-\u03baB in sustaining intestinal epithelial homeostasis beyond inflammation has not been demonstrated. Using NF-\u03baB reporter mice, we detected strong NF-\u03baB activity in Paneth cells, in \u2018+4\/+5\u2019 secretory progenitors and in scattered Lgr5+ crypt base columnar stem cells of small intestinal (SI) crypts. To examine NF\u2013\u03baB functions in SI epithelial self-renewal, mice or SI crypt organoids (\u2018mini-guts\u2019) with ubiquitously suppressed NF-\u03baB activity were used. We show that NF-\u03baB activity is dispensable for maintaining SI epithelial proliferation, but is essential for ex vivo organoid growth. Furthermore, we demonstrate a dramatic reduction of Paneth cells in the absence of NF-\u03baB activity, concomitant with a significant increase in goblet cells and immature intermediate cells. This indicates that NF-\u03baB is required for proper Paneth versus goblet cell differentiation and for SI epithelial homeostasis, which occurs via regulation of Wnt signaling and Sox9 expression downstream of NF-\u03baB. The current study thus presents evidence for an important role for NF-\u03baB in intestinal epithelial self-renewal.<\/jats:p>","DOI":"10.1242\/dev.199683","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T15:21:51Z","timestamp":1636471311000},"source":"Crossref","is-referenced-by-count":21,"title":["NF-\u03baB determines Paneth versus goblet cell fate decision in the small intestine"],"prefix":"10.1242","volume":"148","author":[{"given":"Cristina","family":"Brischetto","sequence":"first","affiliation":[{"name":"Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Krieger","sequence":"additional","affiliation":[{"name":"Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Klotz","sequence":"additional","affiliation":[{"name":"Unit for Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institute (RKI), 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Krahn","sequence":"additional","affiliation":[{"name":"Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-3506","authenticated-orcid":false,"given":"S\u00e9verine","family":"Kunz","sequence":"additional","affiliation":[{"name":"CF Electron Microscopy, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, 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Robert-R\u00f6ssle-Str. 10, 13092 Berlin, Germany"},{"name":"Medical Department, Division of Gastroenterology and Hepatology, Charit\u00e9 University Medicine, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0446-6129","authenticated-orcid":false,"given":"Claus","family":"Scheidereit","sequence":"additional","affiliation":[{"name":"Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-6530","authenticated-orcid":false,"given":"Ruth","family":"Schmidt-Ullrich","sequence":"additional","affiliation":[{"name":"Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center for Molecular Medicine, Robert-R\u00f6ssle-Str. 10, 13092 Berlin, 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