Disruption of zebrafish somite development by pharmacologic inhibition of Hsp90

被引:65
作者
Lele, Z
Hartson, SD
Martin, CC
Whitesell, L
Matts, RL
Krone, PH
机构
[1] Univ Saskatchewan, Dept Anat & Cell Biol, Saskatoon, SK S7N 5E5, Canada
[2] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA
[3] Univ Arizona, Hlth Sci Ctr, Dept Pediat, Tucson, AZ 85724 USA
[4] Univ Arizona, Hlth Sci Ctr, Steele Mem Childrens Res Ctr, Tucson, AZ 85724 USA
基金
加拿大自然科学与工程研究理事会; 美国国家卫生研究院;
关键词
muscle development; zebrafish; Hsp90; geldanamycin; MyoD;
D O I
10.1006/dbio.1999.9262
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Members of the Hsp90 family of molecular chaperones play important roles in allowing some intracellular signaling molecules and transcription factors to reach and maintain functionally active conformations. In the present study, we have utilized the specific Hsp90-binding agent, geldanamycin, to examine the requirement for Hsp90 during zebrafish development. We show that geldanamycin interacts with both the alpha and the beta-isoforms of zebrafish Hsp90 and that geldanamycin-treated embryos consistently exhibit a number of defects in tissues which express either one of these genes. Within the somites, geldanamycin treatment results in the absence of eng-e-expressing muscle pioneer cells. However, early development of adaxial cells, which give rise to muscle pioneers and which strongly express the hsp90 alpha gene shortly before muscle pioneer formation, appeared unaffected. Furthermore, development of the notochord, which provides many of the signals required for proper somite patterning and which does not express detectable levels of either hsp90 alpha or hsp90 beta mRNA, was similarly unaffected in geldanamycin-treated embryos. The data are consistent with there being a temporal and spatial requirement for Hsp90 function within semitic cells which is necessary for the formation of eng-e-expressing muscle pioneers and possibly other striated muscle fiber types. (C) 1999 Academic Press.
引用
收藏
页码:56 / 70
页数:15
相关论文
共 93 条
  • [71] The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin
    Segnitz, B
    Gehring, U
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (30) : 18694 - 18701
  • [72] CONFORMATIONAL ACTIVATION OF A BASIC HELIX-LOOP-HELIX PROTEIN (MYOD1) BY THE C-TERMINAL REGION OF MURINE HSP90 (HSP84)
    SHAKNOVICH, R
    SHUE, GL
    KOHTZ, DS
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (11) : 5059 - 5068
  • [73] SHUE GL, 1994, J BIOL CHEM, V269, P2707
  • [74] STEROID-RECEPTORS AND THEIR ASSOCIATED PROTEINS
    SMITH, DF
    TOFT, DO
    [J]. MOLECULAR ENDOCRINOLOGY, 1993, 7 (01) : 4 - 11
  • [75] SMITH DF, 1995, MOL CELL BIOL, V15, P6804
  • [76] MOLECULAR MARKER ANALYSIS OF GENES-CONTROLLING MORPHOLOGICAL VARIATION IN BRASSICA-RAPA (SYN CAMPESTRIS)
    SONG, K
    SLOCUM, MK
    OSBORN, TC
    [J]. THEORETICAL AND APPLIED GENETICS, 1995, 90 (01) : 1 - 10
  • [77] The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of raf kinase
    Stancato, LF
    Silverstein, AM
    OwensGrillo, JK
    Chow, YH
    Jove, R
    Pratt, WB
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (07) : 4013 - 4020
  • [78] Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent
    Stebbins, CE
    Russo, AA
    Schneider, C
    Rosen, N
    Hartl, FU
    Pavletich, NP
    [J]. CELL, 1997, 89 (02) : 239 - 250
  • [79] AXIAL, A ZEBRAFISH GENE EXPRESSED ALONG THE DEVELOPING BODY AXIS, SHOWS ALTERED EXPRESSION IN CYCLOPS MUTANT EMBRYOS
    STRAHLE, U
    BLADER, P
    HENRIQUE, D
    INGHAM, PW
    [J]. GENES & DEVELOPMENT, 1993, 7 (7B) : 1436 - 1446
  • [80] Nucleotides and two functional states of hsp90
    Sullivan, W
    Stensgard, B
    Caucutt, G
    Bartha, B
    McMahon, N
    Alnemri, ES
    Litwack, G
    Toft, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (12) : 8007 - 8012