Cooperative regulation of growth by Yorkie and Mad through bantam.
The Dpp and Fat-Hippo signaling pathways both regulate growth in Drosophila. Dpp is a BMP family ligand and acts via a Smad family DNA-binding transcription factor, Mad. Fat-Hippo signaling acts via a non-DNA-binding transcriptional coactivator protein, Yorkie. Here, we show that these pathways are directly interlinked. They act synergistically to promote growth, in part via regulation of the microRNA gene bantam, and their ability to promote growth is mutually dependent. Yorkie and Mad physically bind each other, and we identify a 410 bp minimal enhancer of bantam that responds to Yorkie:Mad in vivo and in cultured cells, and show that both Yorkie and Mad associate with this enhancer in vivo. Our results indicate that in promoting the growth of Drosophila tissues, Fat-Hippo and Dpp signaling contribute distinct subunits of a shared transcriptional activation complex, Yorkie:Mad.
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Hyangyee
H
Oh
Kenneth D
KD
Irvine
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000091102:YAP-Signaling Proteins
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D035683:MicroRNAs; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C471146:bantam microRNA, Drosophila
Development. 2008 Sep;135(17):2827-38
18697904
Nat Rev Genet. 2007 Sep;8(9):663-74
17703237
Genes Dev. 2009 Oct 1;23(19):2307-19
19762509
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14897-902
18809931
Genes Dev. 1998 Dec 15;12(24):3900-9
9869643
Cell Cycle. 2009 Jan 1;8(1):49-57
19106601
Dev Cell. 2004 Aug;7(2):229-40
15296719
Dev Biol. 2007 May 1;305(1):187-201
17359963
Cell. 2005 Nov 4;123(3):449-61
16269336
Curr Biol. 2006 Oct 10;16(19):1895-904
16949821
Development. 2004 Sep;131(18):4489-500
15342474
Annu Rev Cell Dev Biol. 2005;21:659-93
16212511
Development. 2008 Dec;135(24):4003-13
19029041
Cell. 2003 Apr 4;113(1):25-36
12679032
Development. 2004 Oct;131(20):4921-30
15371310
Cell. 2006 Aug 25;126(4):767-74
16923395
J Biol Chem. 2001 May 25;276(21):18216-22
11262410
Development. 2002 Feb;129(4):1003-13
11861483
Nat Cell Biol. 2008 Jul;10(7):837-48
18568018
FEBS Lett. 2002 Feb 20;513(1):30-7
11911877
Development. 1998 Apr;125(8):1433-45
9502724
Cancer Res. 2009 Aug 1;69(15):6033-41
19584286
Oncogene. 2002 Jul 25;21(32):4879-84
12118366
Cell. 2007 Sep 21;130(6):1120-33
17889654
Genes Dev. 1998 Dec 15;12(24):3815-20
9869635
Genetics. 2002 Aug;161(4):1527-37
12196398
Nat Struct Mol Biol. 2010 Jan;17(1):69-76
20010841
Dev Cell. 2008 Mar;14(3):377-87
18258485
Oncogene. 2009 Apr 30;28(17):1916-27
19330023
Genes Dev. 2008 Jul 15;22(14):1962-71
18579750
Int J Biochem Cell Biol. 2008;40(3):383-408
18061509
Dev Cell. 2008 Mar;14(3):388-98
18258486
Development. 2008 Mar;135(6):1081-8
18256197
Dev Biol. 2009 Nov 1;335(1):188-97
19733165
Nature. 1997 Jul 17;388(6639):304-8
9230443
Cell. 1996 May 3;85(3):357-68
8616891
Development. 2008 Dec;135(24):4059-69
19004856
Curr Biol. 2008 Mar 25;18(6):435-41
18313299
Dev Cell. 2008 Aug;15(2):309-21
18694569
Trends Cell Biol. 2010 Jul;20(7):410-7
20452772
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6499-503
10823906
Cell. 2003 Apr 18;113(2):221-33
12705870
Cell. 2009 Nov 13;139(4):757-69
19914168