The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation

Kobayashi, M., Nishikawa, K., Suzuki, T., and Yamamoto, M.
Developmental Biology   232(2): 315-326 (Journal)
Registered Authors
Kobayashi, Makoto, Nishikawa, Keizo, Suzuki, Takafumi, Yamamoto, Masayuki
Groucho; Grg3; Six3; Six2; Six4; transcriptional repressor; zebrafish; eye; forebrain
MeSH Terms
  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Conserved Sequence
  • DNA Primers/genetics
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/physiology*
  • Eye/embryology*
  • Eye Proteins
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins/chemistry
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/physiology*
  • Nerve Tissue Proteins/chemistry
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/physiology*
  • Point Mutation
  • Prosencephalon/embryology*
  • Proteins/genetics
  • Proteins/physiology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Repressor Proteins/genetics
  • Repressor Proteins/physiology*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins*
11401394 Full text @ Dev. Biol.
Six3 is a vertebrate homeobox gene that is expressed in the anterior neural plate and eye anlage. We overexpressed a dominant transcriptional activator or repressor form of Six3 in zebrafish embryos to analyze their effect on eye and forebrain formation. RNA injection of the activator form of Six3 into zebrafish embryos caused reduction of the expression domains for rx2, pax2, and emx1 in the anterior neural plate, resulting in eye and forebrain hypoplasia. On the other hand, overexpression of the repressor form of Six3 or wild-type Six3 showed phenotypes opposite to those of the activator form. We found that Six3 has eh1-related motifs, motifs crucial for transcriptional repression function of Drosophila engrailed which plays a role in tethering the Groucho corepressor to the promoters. We isolated one of the zebrafish Groucho family genes, grg3, and demonstrated an interaction between Six3 and Grg3 using yeast two-hybrid analysis. Point-mutations in the eh1-related motifs in Six3 reduced both its eye and forebrain enlarging activities and its interaction with Grg3. These results strongly argue that Six3 functions as a Groucho-dependent repressor in eye and forebrain formation. Furthermore, zebrafish Six2 and Six4 also interacted with Grg3, implying a conserved function among the Six family proteins as transcriptional repressors.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes