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The transcription factor HNF1B is required for the early steps of ureteric bud branching, yet the molecular and cellular events regulated by HNF1B are poorly understood. We report that specific removal of Hnf1b from the ureteric bud leads to defective cell-cell contacts and apicobasal polarity during the early branching events. High-resolution ex vivo imaging combined with a membranous fluorescent reporter strategy show decreased mutant cell rearrangements during mitosis-associated cell dispersal and severe epithelial disorganization. Molecular analysis reveals downregulation of Gdnf-Ret pathway components and suggests that HNF1B acts both upstream and downstream of Ret signaling by directly regulating Gfra1 and Etv5. Subsequently, Hnf1b deletion leads to massively mispatterned ureteric tree network, defective collecting duct differentiation and disrupted tissue architecture, which leads to cystogenesis. Consistently, mRNA-seq analysis shows that the most impacted genes encode intrinsic cell-membrane components with transporter activity. Our study uncovers a fundamental and recurring role of HNF1B in epithelial organization during early ureteric bud branching and in further patterning and differentiation of the collecting duct system in mouse.<\/jats:p>","DOI":"10.1242\/dev.154336","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T10:58:06Z","timestamp":1511261886000},"page":"4704-4719","source":"Crossref","is-referenced-by-count":70,"title":["HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis"],"prefix":"10.1242","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9716-755X","authenticated-orcid":false,"given":"Audrey","family":"Desgrange","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06, IBPS \u2013 UMR7622 1 , F-75005 Paris , France"},{"name":"CNRS, UMR7622, Institut de Biologie Paris-Seine (IBPS) \u2013 Developmental Biology Laboratory 2 , F-75005 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Heliot","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06, IBPS \u2013 UMR7622 1 , F-75005 Paris , France"},{"name":"CNRS, UMR7622, Institut de Biologie Paris-Seine (IBPS) \u2013 Developmental Biology Laboratory 2 , F-75005 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Skovorodkin","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter, University of Oulu; Laboratory of Developmental Biology, Biocenter Oulu and InfoTech, Department of Medical Biochemistry and Molecular Medicine, Oulu Center for Cell Matrix Research, 90220 Oulu 3 , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad U.","family":"Akram","sequence":"additional","affiliation":[{"name":"Center for Machine Vision Research and Signal Analysis (CMVS), University of Oulu 4 , FIN-90014, Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Heikkil\u00e4","sequence":"additional","affiliation":[{"name":"Center for Machine Vision Research and Signal Analysis (CMVS), University of Oulu 4 , FIN-90014, Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli-Pekka","family":"Ronkainen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu, University of Oulu 5 , FIN-90014, Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Miinalainen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu, University of Oulu 5 , FIN-90014, Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo J.","family":"Vainio","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter, University of Oulu; Laboratory of Developmental Biology, Biocenter Oulu and InfoTech, Department of Medical Biochemistry and Molecular Medicine, Oulu Center for Cell Matrix Research, 90220 Oulu 3 , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1562-089X","authenticated-orcid":false,"given":"Silvia","family":"Cereghini","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06, IBPS \u2013 UMR7622 1 , F-75005 Paris , France"},{"name":"CNRS, UMR7622, Institut de Biologie Paris-Seine (IBPS) \u2013 Developmental Biology Laboratory 2 , F-75005 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061215592248700_DEV154336C1","doi-asserted-by":"publisher","first-page":"F839","DOI":"10.1152\/ajprenal.00128.2002","article-title":"Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1beta","volume":"283","author":"Bai","year":"1995","journal-title":"Am. 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