Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus

Nature Genetics
Seung K KimMichael L Cleary

Abstract

Pbx1 is a member of the TALE (three-amino acid loop extension) class of homeodomain transcription factors, which are components of hetero-oligomeric protein complexes thought to regulate developmental gene expression and to maintain differentiated cell states. In vitro studies have shown that Pbx1 regulates the activity of Ipf1 (also known as Pdx1), a ParaHox homeodomain transcription factor required for the development and function of the pancreas in mice and humans. To investigate in vivo roles of Pbx1 in pancreatic development and function, we examined pancreatic Pbx1 expression, and morphogenesis, cell differentiation and function in mice deficient for Pbx1. Pbx1-/- embryos had pancreatic hypoplasia and marked defects in exocrine and endocrine cell differentiation prior to death at embryonic day (E) 15 or E16. In these embryos, expression of Isl1 and Atoh5, essential regulators of pancreatic morphogenesis and differentiation, was severely reduced. Pbx1+/- adults had pancreatic islet malformations, impaired glucose tolerance and hypoinsulinemia. Thus, Pbx1 is essential for normal pancreatic development and function. Analysis of trans-heterozygous Pbx1+/- Ipf1+/- mice revealed in vivo genetic interactions between Pbx1 and Ipf...Continue Reading

References

Nov 5, 1997·Nature Genetics·D A StoffersJ F Habener
Jun 17, 1998·Genes & Development·M HebrokD A Melton
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·S K Kim, D A Melton
Nov 5, 1999·The Journal of Clinical Investigation·W M MacfarlaneA T Hattersley
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GradwohlF Guillemot
Dec 19, 2000·Mechanisms of Development·C A SchnabelM L Cleary
Apr 1, 1962·Developmental Biology·N GOLOSOW, C GROBSTEIN

❮ Previous
Next ❯

Citations

Jan 17, 2009·In Vitro Cellular & Developmental Biology. Animal·Anne S JürgensJürgen S Scheele
Jun 28, 2005·Biochemical and Biophysical Research Communications·Ghaffar MuharramJulie Kerr-Conte
Feb 20, 2003·Developmental Biology·Catherine A SchnabelMichael L Cleary
Aug 30, 2002·Current Opinion in Genetics & Development·Seung K Kim, Raymond J MacDonald
Jul 31, 2003·Current Opinion in Genetics & Development·Maya Kumar, Doug Melton
Feb 20, 2003·Trends in Endocrinology and Metabolism : TEM·Swarup K Chakrabarti, Raghavendra G Mirmira
Jul 19, 2002·Clinical Genetics·K A Johansson, Anne Grapin-Botton
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jiangying LiuDoris A Stoffers
Nov 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yuichi HoriSeung K Kim
Jul 28, 2010·Human Molecular Genetics·Subhabrata ChakrabartiPartha P Majumder
Mar 19, 2004·Pancreas·Satoshi AshizawaXiao-Ping Wang
Apr 2, 2009·Current Opinion in Organ Transplantation·Carmella Evans-MolinaRaghavendra G Mirmira
Aug 5, 2008·Genes & Development·Jennifer M Oliver-Krasinski, Doris A Stoffers
Aug 20, 2005·Development, Growth & Differentiation·Shoen Kume
Jul 23, 2008·Molecular and Cellular Biology·Francesco OrienteFrancesco Beguinot
Sep 19, 2007·Molecular and Cellular Biology·Víctor M DíazFrancesco Blasi
Jun 1, 2004·Molecular and Cellular Biology·Licia SelleriMichael L Cleary
Nov 30, 2005·Molecular and Cellular Biology·Dmitri PenkovFrancesco Blasi
Oct 23, 2003·Annual Review of Cell and Developmental Biology·L Charles Murtaugh, Douglas A Melton
Dec 19, 2002·The Journal of Clinical Investigation·Tadahiro KitamuraDomenico Accili
Jan 25, 2007·Blood·Mrinmoy SanyalMichael L Cleary
Mar 4, 2008·BMC Medical Genetics·Konsta DuesingFernando Gibson
Dec 8, 2009·Journal of Lipid Research·E M SmithM Olivier
Feb 11, 2012·Molecular Endocrinology·Cynthia KhooDoris A Stoffers
Feb 16, 2008·International Journal of Biological Sciences·Anna Rosanas-UrgellGemma Marfany
Oct 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Satyajit K KarnikSeung K Kim
Jun 2, 2012·Journal of Transplantation·Valia Bravo-EganaRicardo L Pastori
Aug 9, 2008·Molecular and Cellular Endocrinology·Andreia S BernardoKevin Docherty
May 20, 2008·Molecular and Cellular Endocrinology·Marie BestKaren Piper Hanley
Oct 26, 2007·Seminars in Cell & Developmental Biology·Kevin DochertyLudovic Vallier
Jul 31, 2007·Molecular Genetics and Metabolism·Daniella A BabuRaghavendra G Mirmira
Jun 13, 2009·Stem Cells·Ken Kwok-Keung ChanAndre Boon-Hwa Choo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.