A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Journal of the American Society of Nephrology : JASN
Annekatrin AueKai M Schmidt-Ott

Abstract

Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrie...Continue Reading

References

Oct 1, 1988·Kidney International·K M MadsenJ W Verlander
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bradley E BernsteinStuart L Schreiber
Sep 28, 2002·Nature·Helena Santos-RosaTony Kouzarides
Oct 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·S Mangan, U Alon
Jan 21, 2006·Developmental Biology·Douglas R MackayXing Dai
Jun 19, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Sawako UnezakiSeiji Ito
Jul 17, 2007·Nature Cell Biology·Michel BagnatDidier Y R Stainier
Feb 28, 2008·Journal of Cell Science·Maithreyi NarasimhaSarah J Bray
Jun 27, 2008·American Journal of Physiology. Cell Physiology·Marion DesclozeauxJennifer L Stow
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
May 19, 2010·The Journal of Cell Biology·Alejo E Rodriguez-FraticelliFernando Martín-Belmonte
Jul 27, 2010·Developmental Biology·Yeliz RifatStephen M Jane
Aug 10, 2010·Current Topics in Developmental Biology·Melissa LittleLorine Wilkinson
Oct 5, 2010·Nature Cell Biology·David M BryantKeith E Mostov
Feb 9, 2011·The Journal of Biological Chemistry·Joanne DurganAlan Hall
Apr 22, 2011·Molecular Biology of the Cell·Liwei JiaMirjam M P Zegers
Mar 2, 2012·Cancer Research·Benjamin CieplySteven M Frisch
Sep 4, 2012·Wiley Interdisciplinary Reviews. Developmental Biology·Frank Costantini
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Xia GaoBrigid L M Hogan
May 27, 2014·Current Opinion in Hematology·Shanti Rojas-SutterlinTrang Hoang

❮ Previous
Next ❯

Citations

Nov 4, 2015·The Journal of Cell Biology·Xia GaoBrigid L M Hogan
Feb 24, 2016·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Denise K Marciano
Jan 19, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Katharina WalentinKai M Schmidt-Ott
Aug 27, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Whitney EdwardsLori T Raetzman
May 2, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lijun MaJianmin Sun
Jun 25, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Mohit Kumar JollySukhwinder Singh Sohal
Jan 9, 2018·Nucleic Acids Research·Qianqian MingUdo Heinemann
Jul 12, 2017·Journal of Dental Research·M R CarpinelliS Dworkin
Aug 25, 2017·Tissue Barriers·Amanda I BaumholtzAimee K Ryan
Jul 18, 2017·Oncogene·S M FrischP M Pifer
Jun 7, 2019·Nature Communications·Evanthia NikolopoulouNicholas D E Greene
Jun 22, 2017·Annals of the New York Academy of Sciences·Felix J Boivin, Kai M Schmidt-Ott
Mar 24, 2016·Oncotarget·Mohit Kumar JollyHerbert Levine
Jun 25, 2020·Pflügers Archiv : European journal of physiology·Alessandro GeniniCarsten A Wagner
Dec 17, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Felix J Boivin, Kai M Schmidt-Ott
Jul 26, 2019·Journal of Dental Research·W ChenM K Kang
Jan 8, 2020·International Journal of Molecular Sciences·Janna Leiz, Kai M Schmidt-Ott
Dec 15, 2017·Journal of the American Society of Nephrology : JASN·Christian HinzeKai M Schmidt-Ott
Nov 27, 2020·Journal of the American Society of Nephrology : JASN·Christian HinzeKai M Schmidt-Ott
Dec 28, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gloria ManzottiAlessia Ciarrocchi
Apr 13, 2021·Veterinary Dermatology·Zihao DengMarina R Carpinelli
Aug 28, 2021·International Journal of Molecular Sciences·Peiya LinSayaka Katagiri
Sep 16, 2020·Cells, Tissues, Organs·Kritika SaxenaMohit Kumar Jolly

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.