title: JAK/STAT signaling is required for hinge growth and patterning in the Drosophila wing disc.
abstract: JAK/STAT signaling is localized to the wing hinge, but its function there is not known. Here we show that the Drosophila STAT Stat92E is downstream of Homothorax and is required for hinge development by cell-autonomously regulating hinge-specific factors. Within the hinge, Stat92E activity becomes restricted to gap domain cells that lack Nubbin and Teashirt. While gap domain cells lacking Stat92E have significantly reduced proliferation, increased JAK/STAT signaling there does not expand this domain. Thus, this pathway is necessary but not sufficient for gap domain growth. We show that reduced Wingless (Wg) signaling dominantly inhibits Stat92E activity in the hinge. However, ectopic JAK/STAT signaling does not perturb Wg expression in the hinge. We report negative interactions between Stat92E and the notum factor Araucan, resulting in restriction of JAK/STAT signaling from the notum. In addition, we find that the distal factor Nub represses the ligand unpaired as well as Stat92E activity. These data suggest that distal expansion of JAK/STAT signaling is deleterious to wing blade development. Indeed, mis-expression of Unpaired within the presumptive wing blade causes small, stunted adult wings. We conclude that JAK/STAT signaling is critical for hinge fate specification and growth of the gap domain and that its restriction to the hinge is required for proper wing development.
authors: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016-6402, USA.
authors: Aidee
authors: A
authors: Ayala-Camargo
authors: Abigail M
authors: AM
authors: Anderson
authors: Marc
authors: M
authors: Amoyel
authors: Aloma B
authors: AB
authors: Rodrigues
authors: Maria Sol
authors: MS
authors: Flaherty
authors: Erika A
authors: EA
authors: Bach
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development*
chemical_list: C099257:ARA protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D014157:Transcription Factors; C104121:nub protein, Drosophila; D053612:Janus Kinases
keywords: Ara; Gap domain; Hinge; Hth; Msh; Nub; Stat92E; Upd; Wg
references: EMBO J. 1994 Oct 3;13(19):4459-68
references: 7925288
references: Development. 2000 Apr;127(7):1499-508
references: 10704395
references: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11405-10
references: 9326622
references: Genes Dev. 1999 Jul 1;13(13):1754-61
references: 10398687
references: Genesis. 2004 Jun;39(2):141-53
references: 15170700
references: Development. 1993 Jun;118(2):401-15
references: 8223268
references: Development. 1999 Nov;126(22):4933-42
references: 10529412
references: Science. 1993 Jan 22;259(5094):484-9
references: 8424170
references: Development. 2007 Aug;134(16):3001-10
references: 17634192
references: Cell. 1991 Jan 11;64(1):63-79
references: 1846092
references: Gene Expr Patterns. 2007 Jan;7(3):323-31
references: 17008134
references: Development. 1995 Feb;121(2):589-99
references: 7768195
references: Development. 2012 Nov;139(21):4051-61
references: 22992954
references: Science. 1998 Jul 17;281(5375):409-13
references: 9665883
references: Development. 2000 May;127(9):1921-9
references: 10751180
references: Dev Cell. 2010 Apr 20;18(4):556-68
references: 20412771
references: Development. 2005 Sep;132(18):4087-96
references: 16093324
references: Dev Dyn. 2009 Jan;238(1):19-28
references: 19097089
references: Genetics. 2003 Nov;165(3):1149-66
references: 14668372
references: Development. 2002 Aug;129(16):3815-23
references: 12135920
references: Dev Biol. 2003 Feb 15;254(2):277-88
references: 12591247
references: Dev Biol. 2000 Dec 15;228(2):287-303
references: 11112330
references: Nat Cell Biol. 2003 Sep;5(9):827-33
references: 12942089
references: Dev Biol. 2009 Apr 15;328(2):445-55
references: 19217893
references: Genes Dev. 2000 Sep 15;14(18):2271-6
references: 10995384
references: PLoS Biol. 2010 Jun 01;8(6):e1000386
references: 20532238
references: Dev Biol. 2007 Jun 15;306(2):760-71
references: 17498684
references: Dev Biol. 2007 Apr 15;304(2):745-58
references: 17313943
references: Development. 2002 Sep;129(17):3995-4004
references: 12163403
references: Curr Biol. 2006 Nov 21;16(22):2206-16
references: 17113384
references: Genetics. 1995 Nov;141(3):1075-86
references: 8582614
references: Development. 2002 Mar;129(5):1273-81
references: 11874922
references: Development. 1993 Apr;117(4):1223-37
references: 8404527
references: Oncogene. 2005 Apr 7;24(15):2503-11
references: 15735706
references: Dev Dyn. 2009 Sep;238(9):2235-53
references: 19504457
references: Development. 2002 Mar;129(6):1369-76
references: 11880346
references: Genes Dev. 1997 Apr 15;11(8):1073-82
references: 9136934
references: Dev Biol. 1975 Feb;42(2):211-21
references: 1116643
references: Development. 2000 Jun;127(12):2685-93
references: 10821766
references: Development. 1997 Feb;124(4):761-71
references: 9043058
references: Curr Opin Genet Dev. 2001 Aug;11(4):470-5
references: 11448635
references: Dev Biol. 2010 Aug 15;344(2):621-36
references: 20501334
references: Development. 1996 Jun;122(6):1781-9
references: 8674417
references: Cell. 1997 Mar 21;88(6):789-99
references: 9118222
references: Development. 2006 Dec;133(23):4721-9
references: 17079268
references: Genes Dev. 1998 Feb 1;12(3):435-46
references: 9450936
references: Development. 2006 Jul;133(14):2605-16
references: 16794031
references: Cell. 1997 Oct 17;91(2):171-83
references: 9346235
references: Dev Dyn. 2007 Oct;236(10):2721-30
references: 17626283
references: Development. 2002 Mar;129(6):1357-68
references: 11880345
references: Dev Biol. 2005 Dec 15;288(2):420-33
references: 16277982
references: Cell. 1996 Apr 5;85(1):95-105
references: 8620542
references: Development. 2009 Mar;136(5):761-9
references: 19176582
references: Dev Biol. 2008 Aug 1;320(1):102-12
references: 18571155
references: Development. 2002 May;129(10):2411-8
references: 11973273