IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas

The EMBO Journal
Georg MellitzerHarry Heimberg

Abstract

Neurogenin 3 (Ngn3) is key for endocrine cell specification in the embryonic pancreas and induction of a neuroendocrine cell differentiation program by misexpression in adult pancreatic duct cells. We identify the gene encoding IA1, a zinc-finger transcription factor, as a direct target of Ngn3 and show that it forms a novel branch in the Ngn3-dependent endocrinogenic transcription factor network. During embryonic development of the pancreas, IA1 and Ngn3 exhibit nearly identical spatio-temporal expression patterns. However, embryos lacking Ngn3 fail to express IA1 in the pancreas. Upon ectopic expression in adult pancreatic duct cells Ngn3 binds to chromatin in the IA1 promoter region and activates transcription. Consistent with this direct effect, IA1 expression is normal in embryos mutant for NeuroD1, Arx, Pax4 and Pax6, regulators operating downstream of Ngn3. IA1 is an effector of Ngn3 function as inhibition of IA1 expression in embryonic pancreas decreases the formation of insulin- and glucagon-positive cells by 40%, while its ectopic expression amplifies neuroendocrine cell differentiation by Ngn3 in adult duct cells. IA1 is therefore a novel Ngn3-regulated factor required for normal differentiation of pancreatic endocri...Continue Reading

References

Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Sep 7, 1999·Nature·A ApelqvistH Edlund
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GradwohlF Guillemot
Apr 11, 2000·Molecular and Cellular Biology·H P HuangM J Tsai
Dec 20, 2002·Mechanisms of Development·Maria E WilsonMichael S German
Feb 27, 2003·The Journal of Biological Chemistry·Hirotaka WatadaMichael S German
Jul 3, 2003·The Journal of Biological Chemistry·Stuart B SmithMichael S German
Oct 17, 2003·Genes & Development·Patrick CollombatPeter Gruss
Dec 31, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jan Jensen
Apr 15, 2004·Developmental Biology·Zhixing LiGeorge K Gittes
Aug 7, 2004·Molecular Endocrinology·Georg MellitzerGérard Gradwohl
Sep 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rosa GasaMichael German
Jul 20, 2005·Developmental Biology·Mercè MartínGérard Gradwohl

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Citations

Aug 21, 2010·Cell Death and Differentiation·J BonnefontK-H Krause
Jul 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Takuya SugiyamaSeung K Kim
Jan 7, 2009·The Journal of Biological Chemistry·Tao ZhangMichael S Lan
Feb 28, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael S Lan, Mary B Breslin
Aug 5, 2008·Genes & Development·Jennifer M Oliver-Krasinski, Doris A Stoffers
Sep 7, 2012·Diabetes, Obesity & Metabolism·O Dumortier, E Van Obberghen
Jun 17, 2010·Hormone Research in Pædiatrics·M HeinisB Duvillié
Apr 15, 2011·The Journal of Clinical Endocrinology and Metabolism·Sara E PinneyDiva D De León
Dec 8, 2010·Disease Models & Mechanisms·Yoshinori ShimajiriMichael S German
Jan 15, 2014·Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation·Anahita ShaerMehrdad Shariati
Nov 14, 2013·Cellular and Molecular Life Sciences : CMLS·David A CanoAnabel Rojas
Jan 18, 2013·ISRN Endocrinology·Ahmed Mansouri
Jan 23, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stéphane CauchiUNKNOWN D.E.S.I.R. Study Group
Aug 17, 2014·Life Sciences·Michael S LanMary B Breslin
Feb 1, 2007·Current Opinion in Organ Transplantation·Claire Bonal, Pedro Luis Herrera
Jan 31, 2008·Neoplasia : an International Journal for Oncology Research·Enrico De SmaeleAlberto Gulino
Nov 30, 2006·Diabetes & Metabolism·G Gradwohl

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