Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate

被引:248
作者
Flynt, Alex S. [1 ]
Li, Nan [1 ]
Thatcher, Elizabeth J. [1 ]
Solnica-Krezel, Lilianna [1 ]
Patton, James G. [1 ]
机构
[1] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA
关键词
D O I
10.1038/ng1953
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Numerous microRNAs ( miRNAs) have been discovered in the genomes of higher eukaryotes, and functional studies indicate that they are important during development. However, little is known concerning the function of individual miRNAs. We approached this problem in zebrafish by combining identification of miRNA expression, functional analyses and experimental validation of potential targets. We show that miR-214 is expressed during early segmentation stages in somites and that varying its expression alters the expression of genes regulated by Hedgehog signaling. Inhibition of miR-214 results in a reduction or loss of slow-muscle cell types. We show that su(fu) mRNA, encoding a negative regulator of Hedgehog signaling, is targeted by miR-214. Through regulation of su( fu), miR-214 enables precise specification of muscle cell types by sharpening cellular responses to Hedgehog.
引用
收藏
页码:259 / 263
页数:5
相关论文
共 22 条
  • [1] Negative regulation of Gli1 and Gli2 activator function by suppressor of fused through multiple mechanisms
    Barnfield, PC
    Zhang, XY
    Thanabalasingham, V
    Yoshida, M
    Hui, CC
    [J]. DIFFERENTIATION, 2005, 73 (08) : 397 - 405
  • [2] Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs
    Bartel, DP
    Chen, CZ
    [J]. NATURE REVIEWS GENETICS, 2004, 5 (05) : 396 - 400
  • [3] The developmental miRNA profiles of zebrafish as determined by small RNA cloning
    Chen, PY
    Manninga, H
    Slanchev, K
    Chien, MC
    Russo, JJ
    Ju, JY
    Sheridan, R
    John, B
    Marks, DS
    Gaidatzis, D
    Sander, C
    Zavolan, M
    Tuschl, T
    [J]. GENES & DEVELOPMENT, 2005, 19 (11) : 1288 - 1293
  • [4] Characterization of the physical interaction of Gli proteins with SUFU proteins
    Dunaeva, M
    Michelson, P
    Kogerman, P
    Toftgard, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (07) : 5116 - 5122
  • [5] Hedgehog acts directly on the zebrafish dermomyotome to promote myogenic differentiation
    Feng, Xuesong
    Adiarte, Eric G.
    Devoto, Stephen H.
    [J]. DEVELOPMENTAL BIOLOGY, 2006, 300 (02) : 736 - 746
  • [6] MicroRNAs regulate brain morphogenesis in zebrafish
    Giraldez, AJ
    Cinalli, RM
    Glasner, ME
    Enright, AJ
    Thomson, JM
    Baskerville, S
    Hammond, SM
    Bartel, DP
    Schier, AF
    [J]. SCIENCE, 2005, 308 (5723) : 833 - 838
  • [7] Conservation of the hedgehog/patched signaling pathway from flies to mice: Induction of a mouse patched gene by Hedgehog
    Goodrich, LV
    Johnson, RL
    Milenkovic, L
    McMahon, JA
    Scott, MP
    [J]. GENES & DEVELOPMENT, 1996, 10 (03) : 301 - 312
  • [8] Zebrafish slow muscle cell migration induces a wave of fast muscle morphogenesis
    Henry, CA
    Amacher, SL
    [J]. DEVELOPMENTAL CELL, 2004, 7 (06) : 917 - 923
  • [9] Hedgehog signalling and the specification of muscle cell identity in the Zebrafish embryo
    Ingham, PW
    Kim, HR
    [J]. EXPERIMENTAL CELL RESEARCH, 2005, 306 (02) : 336 - 342
  • [10] The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway
    Koudijs, MJ
    den Broeder, MJ
    Keijser, A
    Wienholds, E
    Houwing, S
    van Rooijen, EMHC
    Geisler, R
    van Eeden, FJM
    [J]. PLOS GENETICS, 2005, 1 (02): : 223 - 234