University of Oulu

Audrey Desgrange, Claire Heliot, Ilya Skovorodkin, Saad U. Akram, Janne Heikkilä, Veli-Pekka Ronkainen, Ilkka Miinalainen, Seppo J. Vainio, Silvia Cereghini, HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis, Development 2017 144: 4704-4719; doi: 10.1242/dev.154336

HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis

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Author: Desgrange, Audrey1,2; Heliot, Claire1,2; Skovorodkin, Ilya3;
Organizations: 1Sorbonne Universités, UPMC UniversitéParis 06, IBPS –UMR7622, F-75005 Paris, France
2CNRS, UMR7622, Institut de Biologie Paris-Seine (IBPS) – Developmental Biology Laboratory, F-75005 Paris, France
3Faculty 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, Finland
4Center for Machine Vision Research and Signal Analysis (CMVS), University of Oulu, FIN- 90014, Oulu, Finland
5Biocenter Oulu, University of Oulu, FIN-90014, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 29 MB)
Persistent link:
Language: English
Published: Company of Biologists, 2017
Publish Date: 2018-11-20


Kidney development depends crucially on proper ureteric bud branching giving rise to the entire collecting duct system. 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.

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Series: Development
ISSN: 0950-1991
ISSN-E: 1477-9129
ISSN-L: 0950-1991
Volume: 144
Pages: 4704 - 4719
DOI: 10.1242/dev.154336
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
Copyright information: © 2017 The Authors. Published by The Company of Biologists Ltd