ZFIN ID: ZDB-PUB-110128-11
Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry through suppressing fgf8 activity
Xu, P.F., Zhu, K.Y., Jin, Y., Chen, Y., Sun, X.J., Deng, M., Chen, S.J., Chen, Z., and Liu, T.X.
Date: 2010
Source: Proceedings of the National Academy of Sciences of the United States of America   107(6): 2521-2526 (Journal)
Registered Authors: Chen, Yi, Chen, Zhu, Deng, Min, Jin, Yi, Liu, Ting Xi, Sun, Xiao-Jian, Xu, Peng-Fei, Zhu, Kang-Yong
Keywords: set domain, histone methylation, epigenetics, embryonic development, zebrafish
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Body Patterning/genetics*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Fibroblast Growth Factor 8/genetics*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Glycoproteins/genetics
  • Goosecoid Protein/genetics
  • Histone-Lysine N-Methyltransferase/genetics*
  • Homeodomain Proteins/genetics
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins/genetics
  • Molecular Sequence Data
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Sequence Homology, Amino Acid
  • Transcription Factors/genetics
  • Zebrafish Proteins/genetics*
PubMed: 20133783 Full text @ Proc. Natl. Acad. Sci. USA
Dorsal organizer formation is one of the most critical steps in early embryonic development. Several genes and signaling pathways that positively regulate the dorsal organizer development have been identified; however, little is known about the factor(s) that negatively regulates the organizer formation. Here, we show that Setdb2, a SET domain-containing protein possessing potential histone H3K9 methyltransferase activity, restricts dorsal organizer development and regulates left-right asymmetry by suppressing fibroblast growth factor 8 (fgf8) expression. Knockdown of Setdb2 results in a massive expansion of dorsal organizer markers floating head (flh), goosecoid (gsc), and chordin (chd), as well as a significant increase of fgf8, but not fgf4 mRNAs. Consequently, disrupted midline patterning and resultant randomization of left-right asymmetry are observed in Setdb2-deficient embryos. These characteristic changes induced by Setdb2 deficiency can be nearly corrected by either overexpression of a dominant-negative fgf receptor or knockdown of fgf8, suggesting an essential role for Setdb2-Fgf8 signaling in restricting dorsal organizer territory and regulating left-right asymmetry. These results provide unique evidence that a SET domain-containing protein potentially involved in the epigenetic control negatively regulates dorsal organizer formation during early embryonic development.