Wnt9a deficiency discloses a repressive role of Tcf7l2 on endocrine differentiation in the embryonic pancreas

Scientific Reports
G PujadasRosa Gasa

Abstract

Transcriptional and signaling networks establish complex cross-regulatory interactions that drive cellular differentiation during development. Using microarrays we identified the gene encoding the ligand Wnt9a as a candidate target of Neurogenin3, a basic helix-loop-helix transcription factor that functions as a master regulator of pancreatic endocrine differentiation. Here we show that Wnt9a is expressed in the embryonic pancreas and that its deficiency enhances activation of the endocrine transcriptional program and increases the number of endocrine cells at birth. We identify the gene encoding the endocrine transcription factor Nkx2-2 as one of the most upregulated genes in Wnt9a-ablated pancreases and associate its activation to reduced expression of the Wnt effector Tcf7l2. Accordingly, in vitro studies confirm that Tcf7l2 represses activation of Nkx2-2 by Neurogenin3 and inhibits Nkx2-2 expression in differentiated β-cells. Further, we report that Tcf7l2 protein levels decline upon initiation of endocrine differentiation in vivo, disclosing the downregulation of this factor in the developing endocrine compartment. These findings highlight the notion that modulation of signalling cues by lineage-promoting factors is pivota...Continue Reading

References

Nov 2, 2002·Developmental Dynamics : an Official Publication of the American Association of Anatomists·R Scott HellerPalle Serup
Jan 7, 2004·Cancer Cell·Sunil R HingoraniDavid A Tuveson
Aug 26, 2004·Developmental Biology·Martin KunzDietmar Gradl
Sep 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rosa GasaMichael German
Nov 17, 2004·Genes & Development·Juan GalceranRudolf Grosschedl
Apr 5, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Makoto SaegusaIsao Okayasu
Sep 28, 2005·Diabetes·Stella Papadopoulou, Helena Edlund
Sep 30, 2005·Development·L Charles MurtaughDouglas A Melton
Apr 14, 2006·Development·Patrick W HeiserMatthias Hebrok
Jul 1, 2006·Stem Cells·Nathan R TreffJon S Odorico
Jan 16, 2007·BMC Developmental Biology·James M WellsAndrew M Lowy
Apr 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ingrid C RulifsonSeung K Kim
Nov 17, 2007·The EMBO Journal·Seongjin SeoKristen L Kroll
Jan 15, 2008·Development·Penelope HaywardAlfonso Martinez Arias
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Wei TangLawrence Lum
Jan 27, 2009·Diabetes·Gabriela da Silva XavierGuy A Rutter
Dec 17, 2009·BMC Developmental Biology·Keith R AndersonLori Sussel
Feb 2, 2010·Nature Genetics·Kyle J GaultonJorge Ferrer
Jun 10, 2011·Nature·Wilson K ClementsDavid Traver
Nov 25, 2011·Critical Reviews in Eukaryotic Gene Expression·Catherine D Mao, Stephen W Byers

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Citations

Dec 17, 2017·Diabetes·Lina SakhnenyLimor Landsman
Sep 8, 2019·Scientific Reports·Andreas LeihererHeinz Drexel
Feb 8, 2020·Epigenetics & Chromatin·Florian SchmidtMarcel H Schulz
May 28, 2021·Journal of Cellular and Molecular Medicine·Xiaobo NieWei-Dong Chen

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