Back to Search
Start Over
HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis.
- Source :
-
Development (Cambridge, England) [Development] 2017 Dec 15; Vol. 144 (24), pp. 4704-4719. Date of Electronic Publication: 2017 Nov 20. - Publication Year :
- 2017
-
Abstract
- 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.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Cell Adhesion genetics
Cells, Cultured
DNA-Binding Proteins metabolism
Down-Regulation genetics
Glial Cell Line-Derived Neurotrophic Factor metabolism
Glial Cell Line-Derived Neurotrophic Factor Receptors metabolism
Hepatocyte Nuclear Factor 1-beta metabolism
Mice
Mice, Knockout
Nuclear Proteins metabolism
Organ Culture Techniques
PAX2 Transcription Factor biosynthesis
Signal Transduction genetics
Transcription Factors metabolism
Ubiquitin-Protein Ligases
Cell Polarity genetics
Hepatocyte Nuclear Factor 1-beta genetics
Kidney Tubules, Collecting embryology
Ureter embryology
Urogenital Abnormalities embryology
Urogenital Abnormalities genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 144
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 29158444
- Full Text :
- https://doi.org/10.1242/dev.154336