Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.

Human Molecular Genetics
Ishaq A ViringipurampeerC Y Gregory-Evans

Abstract

Tissue fusion is an essential morphogenetic mechanism in development, playing a fundamental role in developing neural tube, palate and the optic fissure. Disruption of genes associated with the tissue fusion can lead to congenital malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For instance, the Pax2 transcription factor is required for optic fissure closure, although the mechanism of Pax2 action leading to tissue fusion remains elusive. This lack of information defining how transcription factors drive tissue morphogenesis at the cellular level is hampering new treatments options. Through loss- and gain-of-function analysis, we now establish that pax2 in combination with vax2 directly regulate the fas-associated death domain (fadd) gene. In the presence of fadd, cell proliferation is restricted in the developing eye through a caspase-dependent pathway. However, the loss of fadd results in a proliferation defect and concomitant activation of the necroptosis pathway through RIP1/RIP3 activity, leading to an abnormal open fissure. Inhibition of RIP1 with the small molecule drug necrostatin-1 rescues the pax2 eye fusion defect, thereby overcoming the underlying genetic defect. Thus, fadd has an essential ...Continue Reading

References

May 1, 1991·Experimental Cell Research·J DelicM Coppey-Moisan
May 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B Grasl-KrauppR Schulte-Hermann
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Apr 1, 1997·Current Biology : CB·M WeilM C Raff
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·A M BarbieriS Banfi
Oct 4, 2000·Nature Genetics·A Nasevicius, S C Ekker
Feb 24, 2001·Age and Ageing·J M Starr
Sep 17, 2002·Current Opinion in Cell Biology·Paul Martin, William Wood
Sep 24, 2004·American Journal of Medical Genetics. Part a·C Y Gregory-EvansK Gregory-Evans
Dec 14, 2004·Journal of Medical Genetics·C Y Gregory-EvansK Gregory-Evans
Apr 23, 2005·American Journal of Human Genetics·Nicola K RaggeIsabel M Hanson
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongxia Z ImtiyazJianke Zhang
Jun 1, 2006·American Journal of Physiology. Renal Physiology·Alison DziarmagaPaul Goodyer
May 26, 2007·Investigative Ophthalmology & Visual Science·Oliver BiehlmaierStephan C F Neuhauss
May 29, 2007·PLoS Genetics·Mara E RobuStephen C Ekker
Aug 1, 2007·Cardiovascular Drugs and Therapy·Christopher C T SmithDerek M Yellon
Apr 15, 2008·Nature Chemical Biology·Alexei DegterevJunying Yuan
May 14, 2008·Archives of Ophthalmology·Panfeng WangQingjiong Zhang
May 16, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cynthia D DugganJohn Ngai
Dec 3, 2008·Neoplasia : an International Journal for Oncology Research·Yahya TamimiPaul Grundy
Feb 18, 2009·Molecular Genetics and Genomics : MGG·Lisette A MaddisonWenbiao Chen
Mar 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bénédicte MascrezManuel Mark
May 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Valentina MassaAndrew J Copp
Jun 9, 2009·Developmental Biology·Enrico MoroFrancesco Argenton
Jul 10, 2009·Methods in Molecular Biology·Leif C LindemanPhilippe Collas
Oct 2, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Baubak BajoghliJoachim Wittbrodt

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Citations

Jan 15, 2014·Cell Death and Differentiation·I A ViringipurampeerC Y Gregory-Evans
Jan 15, 2014·Human Molecular Genetics·Daniel KelbermanJane C Sowden
Sep 27, 2015·Developmental Biology·Jie HuangDavid C Beebe
Nov 7, 2012·Progress in Retinal and Eye Research·Cheryl Y Gregory-EvansKevin Gregory-Evans
Jul 1, 2015·Proteomics. Clinical Applications·Richard D SembaJennifer E Van Eyk
Jun 6, 2015·Birth Defects Research. Part C, Embryo Today : Reviews·Linda M Reis, Elena V Semina
Feb 27, 2015·PLoS Genetics·Brett DemlElena V Semina
May 1, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Natalie Gath, Jeffrey M Gross
Feb 28, 2020·Investigative Ophthalmology & Visual Science·Xiaohe YanUNKNOWN German Mouse Clinic Consortium
Oct 2, 2019·Cancers·José L Marín-RubioMaría Villa-Morales
Jun 25, 2020·Scientific Reports·Megan L WeaverJakub K Famulski
May 1, 2013·Asia-Pacific Journal of Ophthalmology·Benjamin T Whigham, R Rand Allingham
May 11, 2019·Human Genetics·Aisha S ALSomiryKevin Gregory-Evans
Jan 12, 2021·Developmental Biology·Bernadett BoszeNadean L Brown
Jan 29, 2021·Frontiers in Cell and Developmental Biology·Brian Ho Ching ChanJoe Rainger
Aug 4, 2021·Developmental Biology·Mark A Charlton-PerkinsTiffany A Cook
Sep 19, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sarah Lusk, Kristen M Kwan

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