The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage.

Developmental Biology
Kameswaran SurendranRaphael Kopan

Abstract

We previously determined that Notch2, and not Notch1, was required for forming proximal nephron segments. The dominance of Notch2 may be conserved in humans, since Notch2 mutations occur in Alagille syndrome (ALGS) 2 patients, which includes renal complications. To test whether mutations in Notch1 could increase the severity of renal complications in ALGS, we inactivated conditional Notch1 and Notch2 alleles in mice using a Six2-GFP::Cre. This BAC transgene is expressed mosaically in renal epithelial progenitors but uniformly in cells exiting the progenitor pool to undergo mesenchymal-to-epithelial transition. Although delaying Notch2 inactivation had a marginal effect on nephron numbers, it created a sensitized background in which the inactivation of Notch1 severely compromised nephron formation, function, and survival. These and additional observations indicate that Notch1 in concert with Notch2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBP-J-dependent manner. A significant implication is that elevating Notch1 activity could improve renal functions in ALGS2 patients. As proof of principle, we determined that conditional inactivation of Mint, an inhibitor of Notch-RBP-J interaction, resulted ...Continue Reading

References

Dec 18, 2001·Seminars in Liver Disease·D A Piccoli, N B Spinner
Jan 29, 2002·Journal of Neuroscience Research·Maria I GivogriErnesto R Bongarzone
Apr 23, 2002·Nature Immunology·Kenji TanigakiTasuku Honjo
Oct 11, 2002·The EMBO Journal·Franz OswaldRoland M Schmid
Mar 22, 2003·American Journal of Human Genetics·Fengmin LuNancy B Spinner
Jul 30, 2003·Transgenic Research·Jennifer L StratmanTheodore C Simon
Oct 7, 2004·Gene Expression Patterns : GEP·Tino D PiscioneSusan E Quaggin
Apr 12, 2005·American Journal of Physiology. Renal Physiology·Linghong Chen, Qais Al-Awqati
Jul 19, 2005·Nature·Vidu GargDeepak Srivastava
Jul 7, 2006·Annual Review of Cell and Developmental Biology·Gregory R Dressler
Jan 12, 2007·Development·Marc VooijsRaphael Kopan
Jan 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Masayuki TsujiTasuku Honjo
Jan 31, 2007·The Journal of Experimental Medicine·Valerie BesseyriasFreddy Radtke
Apr 3, 2007·Biophysical Journal·Joseph LevineLeonid Mirny
Apr 19, 2007·Nature Immunology·Kenji Tanigaki, Tasuku Honjo
Apr 26, 2007·Genesis : the Journal of Genetics and Development·Daisuke YabeTasuku Honjo
Jun 15, 2007·Journal of the American Society of Nephrology : JASN·Raphael KopanKameswaran Surendran
Dec 25, 2007·Journal of Molecular Biology·Cristina Del BiancoStephen C Blacklow
Dec 25, 2007·The Journal of Biological Chemistry·Shuting BaiSteven L Teitelbaum
Mar 12, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Prajakta VaradkarBrent McCright
Mar 29, 2008·Cell Stem Cell·Benjamin D HumphreysJoseph V Bonventre
Apr 3, 2008·The Journal of Biological Chemistry·David R FriedmannRhett A Kovall
Jul 31, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fabian GeislerJens T Siveke
Apr 22, 2009·Cell·Raphael Kopan, Maria Xenia G Ilagan

❮ Previous
Next ❯

Citations

Nov 26, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Raphael KopanZhenyi Liu
Apr 10, 2010·Journal of the American Society of Nephrology : JASN·Kameswaran SurendranRaphael Kopan
Jun 10, 2011·Development·Simon D HardingDuncan Davidson
Jun 28, 2011·Journal of the American Society of Nephrology : JASN·Kameswaran Surendran, Raphael Kopan
Aug 31, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Agnieszka Swiatecka-Urban
Mar 19, 2011·Biochemical and Biophysical Research Communications·Jianxun HanMichael J Hendzel
Aug 11, 2011·Journal of Cellular Physiology·Gavino FaaVassilios Fanos
Nov 7, 2012·Journal of Cellular Biochemistry·Feng GaoHuijun Duan
May 13, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Donal MacGroganJosé Luis de la Pompa
Sep 29, 2011·The Journal of Pathology·Yasemin Sirin, Katalin Susztak
Nov 23, 2011·American Journal of Medical Genetics. Part a·Binita M KamathKevin Meyers
Jun 17, 2015·Stem Cells International·Aleksandra Rak-RaszewskaSeppo Vainio
Sep 10, 2014·International Urology and Nephrology·Vassilios FanosGavino Faa
Apr 10, 2007·Trends in Cardiovascular Medicine·Thierry Pedrazzini
Nov 10, 2015·Gene·Christopher M GrochowskiNancy B Spinner
Nov 3, 2016·Development·Eunah ChungJoo-Seop Park
Aug 21, 2012·Journal of the American Society of Nephrology : JASN·Robert M KaoAndrew P McMahon
Oct 3, 2019·Genes & Development·Melissa H Little, Alexander N Combes
Dec 31, 2019·Development, Growth & Differentiation·Katsuto Hozumi
Jun 25, 2020·Pflügers Archiv : European journal of physiology·Alessandro GeniniCarsten A Wagner
Jun 1, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Malini MukherjeeKameswaran Surendran
Nov 7, 2019·Scientific Reports·Patrick DeaconJoo-Seop Park
Nov 7, 2019·Biomolecules·Malini MukherjeeKameswaran Surendran
Aug 9, 2020·Journal of the American Society of Nephrology : JASN·Sierra S MarableJoo-Seop Park
Feb 6, 2017·Journal of Cellular and Molecular Medicine·Chuyue ZhangZhuo Yang
Feb 2, 2021·Frontiers in Pharmacology·Carlamaria ZojaDaniela Macconi
Oct 5, 2010·Organogenesis·Jordan A Kreidberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alagille Syndrome

Alagille syndrome is a multi-system genetic disorder that can affect the liver, heart, and other parts of the body. It’s characterization includes heart problems, liver damage, jaundice, and xanthomas. Here is the latest research.