title: Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila.
abstract: Planar cell polarity (PCP) is cellular polarity within the plane of an epithelial tissue or organ. PCP is established through interactions of the core Frizzled (Fz)/PCP factors and, although their molecular interactions are beginning to be understood, the upstream input providing the directional bias and polarity axis remains unknown. Among core PCP genes, Fz is unique as it regulates PCP both cell-autonomously and non-autonomously, with its extracellular domain acting as a ligand for Van Gogh (Vang). We demonstrate in Drosophila melanogaster wings that Wg (Wingless) and dWnt4 (Drosophila Wnt homologue) provide instructive regulatory input for PCP axis determination, establishing polarity axes along their graded distribution and perpendicular to their expression domain borders. Loss-of-function studies reveal that Wg and dWnt4 act redundantly in PCP determination. They affect PCP by modulating the intercellular interaction between Fz and Vang, which is thought to be a key step in setting up initial polarity, thus providing directionality to the PCP process.
authors.affiliation: Department of Developmental and Regenerative Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Angel-Carlos
authors.initials: AC
authors.lastname: Roman
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Carvajal-Gonzalez
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D008565:Membrane Proteins; C111638:Vang protein, Drosophila; D051153:Wnt Proteins; D051155:Wnt1 Protein; C454442:Wnt4 protein, Drosophila; C074622:wg protein, Drosophila
references.citation: Dev Biol. 1994 Oct;165(2):716-26
references.pmid: 7958432
references.citation: Dev Cell. 2011 Feb 15;20(2):163-76
references.pmid: 21316585
references.citation: PLoS Biol. 2010 Jun 01;8(6):e1000386
references.pmid: 20532238
references.citation: Cell. 1999 Mar 19;96(6):833-45
references.pmid: 10102271
references.citation: Nature. 1996 May 23;381(6580):316-8
references.pmid: 8692268
references.citation: Dev Biol. 2001 Apr 15;232(2):339-50
references.pmid: 11401396
references.citation: Development. 2011 Jul;138(13):2751-9
references.pmid: 21613320
references.citation: Development. 2004 Oct;131(19):4651-64
references.pmid: 15329345
references.citation: Dev Cell. 2002 May;2(5):525-35
references.pmid: 12015961
references.citation: Mech Dev. 2001 May;103(1-2):117-20
references.pmid: 11335117
references.citation: Nat Rev Genet. 2007 Feb;8(2):126-38
references.pmid: 17230199
references.citation: Dev Cell. 2008 Sep;15(3):462-469
references.pmid: 18804440
references.citation: Development. 2004 Sep;131(18):4489-500
references.pmid: 15342474
references.citation: Dev Cell. 2002 Dec;3(6):851-63
references.pmid: 12479810
references.citation: J Embryol Exp Morphol. 1982 Apr;68:37-57
references.pmid: 6809878
references.citation: Development. 1994 Dec;120(12):3355-9
references.pmid: 7821207
references.citation: Dev Biol. 1994 Mar;162(1):229-44
references.pmid: 8125190
references.citation: Nat Neurosci. 2006 Jan;9(1):67-75
references.pmid: 16369482
references.citation: Science. 1996 Sep 6;273(5280):1373-7
references.pmid: 8703069
references.citation: Cell. 2010 Sep 3;142(5):773-86
references.pmid: 20813263
references.citation: Cell. 1996 Nov 29;87(5):833-44
references.pmid: 8945511
references.citation: Nature. 2003 Jan 30;421(6922):543-7
references.pmid: 12540853
references.citation: Cell. 2007 Jun 15;129(6):1051-63
references.pmid: 17574020
references.citation: Dev Cell. 2002 Apr;2(4):437-48
references.pmid: 11970894
references.citation: Cell. 1999 Sep 3;98(5):585-95
references.pmid: 10490098
references.citation: Curr Biol. 1997 Dec 1;7(12):940-9
references.pmid: 9382848
references.citation: Dev Cell. 2011 Apr 19;20(4):511-25
references.pmid: 21497763
references.citation: Nature. 2009 Jan 29;457(7229):589-93
references.pmid: 18987628
references.citation: Development. 2011 May;138(10):1877-92
references.pmid: 21521735
references.citation: EMBO J. 1993 Dec 15;12(13):5293-302
references.pmid: 8262072
references.citation: Dev Biol. 1997 May 15;185(2):244-60
references.pmid: 9187086
references.citation: Cell. 1998 May 29;93(5):767-77
references.pmid: 9630221
references.citation: Mech Dev. 2003 Apr;120(4):467-76
references.pmid: 12676324
references.citation: Curr Biol. 2012 Jul 24;22(14):1296-301
references.pmid: 22727699
references.citation: Science. 2005 Jan 21;307(5708):423-6
references.pmid: 15662015
references.citation: Mech Dev. 2000 Jun;94(1-2):47-56
references.pmid: 10842058
references.citation: Development. 1997 Feb;124(4):871-80
references.pmid: 9043068
references.citation: Cell. 2008 Jun 13;133(6):1093-105
references.pmid: 18555784
references.citation: Development. 1995 Sep;121(9):3045-55
references.pmid: 7555730
references.citation: Development. 2006 Nov;133(22):4561-72
references.pmid: 17075008
references.citation: Nat Rev Genet. 2007 Jul;8(7):555-63
references.pmid: 17563758
references.citation: Development. 2012 Oct;139(19):3665-74
references.pmid: 22949620
references.citation: Science. 2000 Jun 9;288(5472):1825-8
references.pmid: 10846164
references.citation: Genetics. 1990 Apr;124(4):889-97
references.pmid: 2108904
references.citation: Annu Rev Cell Dev Biol. 2005;21:155-76
references.pmid: 16212491
references.citation: Genesis. 2005 Jul;42(3):150-61
references.pmid: 15986451
references.citation: Neural Dev. 2009 Feb 11;4:7
references.pmid: 19210786
references.citation: Cell. 2002 Mar 8;108(5):675-88
references.pmid: 11893338
references.citation: Curr Biol. 2008 Oct 28;18(20):1555-64
references.pmid: 18804371
references.citation: Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R227-34
references.pmid: 16987888
references.citation: Development. 2002 Jun;129(11):2749-60
references.pmid: 12015301
references.citation: Development. 2007 Feb;134(4):647-58
references.pmid: 17259302
references.citation: Development. 1994 Mar;120(3):621-36
references.pmid: 8162860
references.citation: Genetics. 1996 Jan;142(1):205-15
references.pmid: 8770598
references.citation: Annu Rev Genet. 2008;42:517-40
references.pmid: 18710302
references.citation: Development. 1993 Jun;118(2):401-15
references.pmid: 8223268
references.citation: Nat Cell Biol. 2008 Nov;10(11):1257-68
references.pmid: 18849982
references.citation: Development. 2000 May;127(10):2227-38
references.pmid: 10769246
references.citation: Nature. 2000 May 4;405(6782):76-81
references.pmid: 10811221
references.citation: Curr Biol. 2008 Oct 28;18(20):R959-61
references.pmid: 18957252
references.citation: Dev Cell. 2008 Aug;15(2):309-21
references.pmid: 18694569
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15961-6
references.pmid: 15514021
references.citation: Trends Cell Biol. 2009 Jul;19(7):295-305
references.pmid: 19560358
references.citation: J Biol Chem. 2002 Nov 1;277(44):41762-9
references.pmid: 12205098
references.citation: Science. 1993 Jan 22;259(5094):484-9
references.pmid: 8424170