Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1

Dev Biol. 2014 Aug 15;392(2):233-44. doi: 10.1016/j.ydbio.2014.05.022. Epub 2014 Jun 2.


As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-β superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.

Keywords: Convergence and extension; Dvr1; Histone methylation; Setdb2; TGF-β superfamily; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Movement / physiology*
  • Fluorescent Antibody Technique
  • Gastrulation / physiology*
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Knockdown Techniques
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histone-Lysine N-Methyltransferase / physiology*
  • In Situ Hybridization
  • Microarray Analysis
  • Morpholinos / genetics
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Zebrafish / embryology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • Zebrafish Proteins / physiology*


  • Gdf3 protein, zebrafish
  • Morpholinos
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Setdb2 protein, zebrafish