Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling

Development
Pedro P RochaHeinrich Schrewe

Abstract

The Mediator complex is commonly seen as a molecular bridge that connects DNA-bound transcription factors to the RNA polymerase II (Pol II) machinery. It is a large complex of 30 subunits that is present in all eukaryotes. The Med12 subunit has been implicated not only in the regulation of Pol II activity, but also in the binding of transcription factors to the bulk of the Mediator complex. We targeted Med12 in mouse embryonic stem cells to investigate the in vivo function of this subunit. We report here the developmental defects of Med12 hypomorphic mutants that have a drastic reduction in Med12 protein levels. These mutants fail to develop beyond embryonic day 10 and have severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. We show that in Med12 hypomorphic embryos, the Wnt/planar cell polarity pathway is disrupted and that canonical Wnt/beta-catenin signaling is impaired. In agreement with this, embryos that are incapable of Med12 expression failed to establish the anterior visceral endoderm or activate brachyury expression, and did not complete gastrulation.

References

Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·J P DiSantoK Rajewsky
Jan 5, 2000·Genes & Development·T P YamaguchiA P McMahon
Feb 9, 2000·The Journal of Cell Biology·J HuelskenW Birchmeier
Sep 19, 2000·Nature·S AkoulitchevD Reinberg
Jul 24, 2002·Nucleic Acids Research·Rongjia ZhouSchomber Tibor
Mar 15, 2003·Developmental Cell·Alexander AulehlaBernhard G Herrmann
May 4, 2004·Nature Reviews. Molecular Cell Biology·Dylan J TaatjesRobert Tjian
May 18, 2005·Trends in Biochemical Sciences·Ronald C ConawayJoan W Conaway
May 18, 2005·Trends in Biochemical Sciences·Sohail Malik, Robert G Roeder
Nov 3, 2005·The Journal of Biological Chemistry·Yuichiro Takagi, Roger D Kornberg
Dec 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sung-Kook HongNeil A Hukriede
Mar 28, 2006·The Journal of Biological Chemistry·Seokjoong KimThomas G Boyer
Sep 20, 2006·Neuron·Frédérique VaroqueauxNils Brose
Sep 27, 2006·Molecular and Cellular Biology·Haiying ZhouThomas G Boyer
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hans ElmlundClaes M Gustafsson
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Xiaoqun WangSu Guo
Dec 21, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Muriel J Harris, Diana M Juriloff
Jan 30, 2007·Development·Yanshu Wang, Jeremy Nathans
Mar 6, 2007·Nature Genetics·Hiba RishegMichael J Friez
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sophia H L GeorgeAndras Nagy
Mar 21, 2007·Journal of Medical Genetics·Charles E SchwartzRoger E Stevenson
Apr 5, 2007·Nature Protocols·Guy S Eakin, Anna-Katerina Hadjantonakis
Jul 7, 2007·Molecular Cell·Aaron Joseph DonnerJoaquin Maximiliano Espinosa
Jul 11, 2007·Molecular and Cellular Biology·Thomas WesterlingTomi P Mäkelä
Apr 9, 2008·Developmental Biology·Chong Hyun ShinDidier Y R Stainier
Nov 28, 2008·The Journal of Biological Chemistry·Antonin V TutterShilpa Kadam
Apr 22, 2009·Cell·Masahiro NarimatsuJeffrey L Wrana
Apr 28, 2009·Development·Valerie WilsonKate G Storey

❮ Previous
Next ❯

Citations

May 20, 2011·Nature·Mark E Lindsay, Harry C Dietz
Oct 4, 2013·The New England Journal of Medicine·Serdar E Bulun
Oct 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Haiying ZhouThomas G Boyer
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Masanori OnoSerdar E Bulun
Dec 23, 2011·Genes & Development·Tomas ValentaKonrad Basler
Sep 9, 2011·PloS One·Maria-Cristina KeightleyGraham J Lieschke
Jul 7, 2012·PloS One·Gaëlle PérotFrédéric Chibon
Oct 11, 2012·PloS One·Dafne Pérez-MontareloAntonio Reverter
Apr 23, 2014·Biochimica Et Biophysica Acta·Concetta SchianoClaudio Napoli
Aug 22, 2012·Annual Review of Cell and Developmental Biology·John B Wallingford
Apr 8, 2015·American Journal of Medical Genetics. Part a·Aditi TrehanCynthia J Tifft
Jul 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ji-Hoon LeeEric N Olson
Mar 20, 2015·American Journal of Medical Genetics. Part a·Jesse M HunterLisa Baumbach-Reardon
Feb 19, 2014·Fertility and Sterility·Masanori OnoSerdar E Bulun
Apr 8, 2014·Chemical Reviews·Monika FuxreiterVladimir N Uversky
Jan 10, 2012·International Journal of Cancer. Journal International Du Cancer·Dominique Nadine MarkowskiJörn Bullerdiek
Jul 28, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Florence Janody, Jessica E Treisman
Jul 21, 2015·The Journal of Clinical Investigation·Priya MittalAleksandar Rajkovic
Jun 4, 2013·Genomics, Proteomics & Bioinformatics·Chad E Grueter
Oct 29, 2013·Obstetrics and Gynecology International·Andrea CiavattiniPasquapina Ciarmela
Aug 16, 2011·Seminars in Cell & Developmental Biology·Jason M SpaethThomas G Boyer
Jun 4, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sabrina Croce, Frédéric Chibon
Jul 5, 2015·BMC Genomics·M Elizabeth O LockeKathleen A Hill
Mar 7, 2015·Trends in Genetics : TIG·Phillip Grote, Bernhard G Herrmann
Aug 23, 2011·Seminars in Cell & Developmental Biology·Kathryn E Hentges
Oct 11, 2011·Biochimie·Claudio NapoliAmelia Casamassimi
Oct 19, 2014·Molecular Genetics and Genomics : MGG·Sunil K HalderAyman Al-Hendy
Feb 19, 2015·Nature Reviews. Molecular Cell Biology·Benjamin L Allen, Dylan J Taatjes
May 18, 2016·BMC Developmental Biology·Nam Hee KimThomas G Boyer
Jun 12, 2016·Developmental Biology·Manuel Buendía-Monreal, C Stewart Gillmor
Jan 28, 2016·Journal of Cellular Biochemistry·Babajan BanaganapalliNoor Ahmad Shaik
Jan 6, 2017·International Journal of Molecular Sciences·Meng GuoChen Liu
Nov 8, 2014·Biology of Reproduction·Masanori OnoTetsuo Maruyama
Mar 8, 2017·Molecular Oncology·Felipe C GeyerBritta Weigelt
Jun 28, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Dana DvorskáJozef Višňovský

❮ Previous
Next ❯

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