Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors

被引:82
作者
Knirr, S [1 ]
Frasch, M [1 ]
机构
[1] Mt Sinai Sch Med, Dept Biochem & Mol Biol, New York, NY 10029 USA
关键词
muscle founders; pericardial cells; heart; even-skipped; induction; enhancer;
D O I
10.1006/dbio.2001.0397
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Individual somatic muscles and heart progenitors are specified at defined positions within the mesodermal layer of Drosophila. The expression of the homeobox gene even-skipped (eve) identifies one specific subset of cells in the dorsal mesoderm, which give rise to particular pericardial cells and dorsal body wall muscles. Genetic analysis has shown that the induction of eve in these cells involves the combined activities of genes encoding mesoderm-intrinsic factors, such as Tinman (Tin), and spatially restricted signaling activities that are largely derived from the ectoderm, particularly those encoded by wingless (wg) and decapentaplegic (dpp). Here we show that a Dpp-activated Smad protein, phosphorylated Mad, is colocalized in eve-expressing cells during an extended developmental period. We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo. This enhancer also contains a number of binding sites for the Wg-effector Pangolin (Pan/Lef-1), which are required for full levels of enhancer activity. However, we find that their main function is to prevent ectopic enhancer activity in the dorsal mesoderm. This suggests that, in the absence of Wg signaling, Pan binding serves to abrogate the synergistic activities of Smads and Tin in eve activation while, in cells that receive Wg signals, Pan is converted into a coactivator that promotes eve induction. Together, these data show that the eve enhancer integrates several regulatory pathways via the combinatorial binding of the mesoderm-intrinsic regulator Tin and the effectors of the Dpp and Wg signals. (C) 2001 Academic Press.
引用
收藏
页码:13 / 26
页数:14
相关论文
共 56 条
  • [11] Drosophila Tcf and Groucho interact to repress Wingless signalling activity
    Cavallo, RA
    Cox, RT
    Moline, MM
    Roose, J
    Polevoy, GA
    Clevers, H
    Peifer, M
    Bejsovec, A
    [J]. NATURE, 1998, 395 (6702) : 604 - 608
  • [12] Das P, 1998, DEVELOPMENT, V125, P1519
  • [13] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene
    Dennler, S
    Itoh, S
    Vivien, D
    ten Dijke, P
    Huet, S
    Gauthier, JM
    [J]. EMBO JOURNAL, 1998, 17 (11) : 3091 - 3100
  • [14] THE DROSOPHILA ZFH-1 AND ZFH-2 GENES ENCODE NOVEL PROTEINS CONTAINING BOTH ZINC-FINGER AND HOMEODOMAIN MOTIFS
    FORTINI, ME
    LAI, ZC
    RUBIN, GM
    [J]. MECHANISMS OF DEVELOPMENT, 1991, 34 (2-3) : 113 - 122
  • [15] Frasch M, 1999, ADV D BIOCH, V5, P1, DOI 10.1016/S1064-2722(08)60015-8
  • [16] CHARACTERIZATION AND LOCALIZATION OF THE EVEN-SKIPPED PROTEIN OF DROSOPHILA
    FRASCH, M
    HOEY, T
    RUSHLOW, C
    DOYLE, H
    LEVINE, M
    [J]. EMBO JOURNAL, 1987, 6 (03) : 749 - 759
  • [17] Intersecting signalling and transcriptional pathways in Drosophila heart specification
    Frasch, M
    [J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 1999, 10 (01) : 61 - 71
  • [18] INDUCTION OF VISCERAL AND CARDIAC MESODERM BY ECTODERMAL DPP IN THE EARLY DROSOPHILA EMBRYO
    FRASCH, M
    [J]. NATURE, 1995, 374 (6521) : 464 - 467
  • [19] Fujioka M, 1999, DEVELOPMENT, V126, P2527
  • [20] D-mef2 is a target for Tinman activation during Drosophila heart development
    Gajewski, K
    Kim, Y
    Lee, YM
    Olson, EN
    Schulz, RA
    [J]. EMBO JOURNAL, 1997, 16 (03) : 515 - 522