title: Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells.
abstract: Wnt signaling has multiple dynamic roles during development of the gastrointestinal and respiratory systems. Differential Wnt signaling is thought to be a critical step in Xenopus endoderm patterning such that during late gastrula and early somite stages of embryogenesis, Wnt activity must be suppressed in the anterior to allow the specification of foregut progenitors. However, the foregut endoderm also expresses the Wnt-receptor Frizzled 7 (Fzd7) as well as several Wnt ligands suggesting that the current model may be too simple. In this study, we show that Fzd7 is required to transduce a low level of Wnt signaling that is essential to maintain foregut progenitors. Foregut-specific Fzd7-depletion from the Xenopus foregut resulted in liver and pancreas agenesis. Fzd7-depleted embryos failed to maintain the foregut progenitor marker hhex and exhibited decreased proliferation; in addition the foregut cells were enlarged with a randomized orientation. We show that in the foregut Fzd7 signals via both the Wnt/β-catenin and Wnt/JNK pathways and that different thresholds of Wnt-Fzd7 activity coordinate progenitor cell fate, proliferation and morphogenesis.
authors.affiliation: Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center and the College of Medicine, University of Cincinnati, Cincinnati OH 45229, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rankin
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Zorn
mesh_terms: D000818:Animals; D019521:Body Patterning; D019070:Cell Lineage; D049109:Cell Proliferation; D004707:Endoderm / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis; D051176:beta Catenin / Q000378:metabolism
chemical_list: C492040:Fzd7 protein, Xenopus; D018398:Homeodomain Proteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C513078:hhex protein, Xenopus; C099992:ventx2.1 protein, Xenopus; D048670:MAP Kinase Kinase 4
references.citation: Cell. 2006 Nov 3;127(3):469-80
references.pmid: 17081971
references.citation: Dev Cell. 2009 Jul;17(1):9-26
references.pmid: 19619488
references.citation: Dev Dyn. 2009 Dec;238(12):3111-25
references.pmid: 19924810
references.citation: Nat Biotechnol. 2008 Apr;26(4):443-52
references.pmid: 18288110
references.citation: Development. 2011 Apr;138(7):1339-48
references.pmid: 21385764
references.citation: Dev Cell. 2005 Oct;9(4):555-64
references.pmid: 16198297
references.citation: Dev Cell. 2002 Apr;2(4):449-61
references.pmid: 11970895
references.citation: Dev Dyn. 2011 Mar;240(3):486-500
references.pmid: 21337461
references.citation: Dev Dyn. 2000 Aug;218(4):671-80
references.pmid: 10906785
references.citation: Dev Dyn. 2005 Apr;232(4):958-68
references.pmid: 15739222
references.citation: J Cell Biol. 2008 Sep 22;182(6):1073-82
references.pmid: 18809723
references.citation: Nat Rev Genet. 2007 Feb;8(2):126-38
references.pmid: 17230199
references.citation: Dev Growth Differ. 2000 Aug;42(4):347-57
references.pmid: 10969734
references.citation: Cell. 2000 Jan 21;100(2):209-19
references.pmid: 10660044
references.citation: Development. 2004 Jul;131(13):3069-80
references.pmid: 15163629
references.citation: Cell. 1999 Nov 24;99(5):499-510
references.pmid: 10589678
references.citation: Development. 2008 Nov;135(22):3719-29
references.pmid: 18927149
references.citation: Dev Biol. 2011 Mar 15;351(2):297-310
references.pmid: 21215263
references.citation: Development. 2005 Oct;132(20):4421-36
references.pmid: 16192308
references.citation: Hepatology. 2010 Jan;51(1):297-305
references.pmid: 19998274
references.citation: Organogenesis. 2008 Apr;4(2):81-6
references.pmid: 18953422
references.citation: Genes Dev. 2008 Nov 1;22(21):3050-63
references.pmid: 18981481
references.citation: Dev Cell. 2002 Sep;3(3):367-81
references.pmid: 12361600
references.citation: Cell. 1999 Sep 3;98(5):585-95
references.pmid: 10490098
references.citation: Genesis. 2001 Jul;30(3):119-22
references.pmid: 11477687
references.citation: Nature. 2009 Oct 1;461(7264):614-20
references.pmid: 19759537
references.citation: Development. 2007 Jul;134(14):2651-61
references.pmid: 17567666
references.citation: Development. 2009 Dec;136(24):4083-8
references.pmid: 19906850
references.citation: Nat Rev Genet. 2008 May;9(5):329-40
references.pmid: 18398419
references.citation: Science. 2009 Jun 26;324(5935):1707-10
references.pmid: 19556507
references.citation: J Cell Biol. 1996 Dec;135(6 Pt 2):1899-911
references.pmid: 8991100
references.citation: Dev Biol. 2009 Mar 15;327(2):386-98
references.pmid: 19138684
references.citation: Cell. 2005 Mar 25;120(6):857-71
references.pmid: 15797385
references.citation: Development. 2005 Jan;132(1):35-47
references.pmid: 15576401
references.citation: FASEB J. 2011 Feb;25(2):613-23
references.pmid: 21030692
references.citation: Nat Med. 2004 Jan;10(1):55-63
references.pmid: 14702635
references.citation: EMBO J. 2004 Aug 18;23(16):3249-58
references.pmid: 15272309
references.citation: Development. 2000 Jul;127(14):3091-100
references.pmid: 10862746
references.citation: Int Rev Cytol. 2007;259:49-111
references.pmid: 17425939
references.citation: J Cell Biol. 2006 Dec 4;175(5):791-802
references.pmid: 17130287
references.citation: Dev Cell. 2007 May;12(5):779-92
references.pmid: 17488628
references.citation: Dev Cell. 2009 Aug;17(2):290-8
references.pmid: 19686689
references.citation: Dev Growth Differ. 2011 Oct;53(8):911-23
references.pmid: 21995331
references.citation: PLoS Biol. 2006 Apr;4(4):e115
references.pmid: 16602827
references.citation: Nature. 2001 Oct 25;413(6858):856-60
references.pmid: 11677610
references.citation: Mech Dev. 1999 Aug;86(1-2):203-7
references.pmid: 10446283
references.citation: Mech Dev. 2000 Apr;92(2):227-37
references.pmid: 10727861
references.citation: Dev Biol. 2001 Nov 1;239(1):148-60
references.pmid: 11784025
references.citation: Development. 2011 Aug;138(16):3557-68
references.pmid: 21771809
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16313-8
references.pmid: 17060633
references.citation: Cardiovasc Res. 2010 Jan 1;85(1):100-9
references.pmid: 19622544
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15436-41
references.pmid: 17881570
references.citation: Curr Biol. 2009 Sep 29;19(18):1573-80
references.pmid: 19747829
references.citation: Development. 2000 May;127(9):1981-90
references.pmid: 10751186
references.citation: J Cell Biol. 2004 Dec 20;167(6):1183-94
references.pmid: 15596540
references.citation: Development. 2007 Jun;134(12):2207-17
references.pmid: 17507400
references.citation: Development. 2006 Nov;133(22):4399-408
references.pmid: 17035295
references.citation: Genes Dev. 2009 Feb 1;23(3):265-77
references.pmid: 19204114
references.citation: Annu Rev Genet. 2005;39:561-613
references.pmid: 16285872
references.citation: Dev Biol. 1987 Aug;122(2):300-19
references.pmid: 3596014
references.citation: Dev Biol. 2008 Aug 1;320(1):161-74
references.pmid: 18585699
references.citation: J Cell Biol. 2003 Sep 1;162(5):899-908
references.pmid: 12952940
references.citation: Organogenesis. 2008 Apr;4(2):87-91
references.pmid: 19279719
references.citation: Nature. 2011 Feb 3;470(7332):105-9
references.pmid: 21151107
references.citation: Dev Biol. 1999 May 15;209(2):282-97
references.pmid: 10328921
references.citation: Genes Dev. 2010 Nov 15;24(22):2517-30
references.pmid: 21078818
references.citation: Nature. 2006 Aug 10;442(7103):688-91
references.pmid: 16799568
references.citation: Annu Rev Cell Dev Biol. 2009;25:221-51
references.pmid: 19575677