Lhx2 mediates the activity of Six3 in zebrafish forebrain growth

Hideki Ando, Makoto Kobayashi, Tatsuya Tsubokawa, Keiichi Uyemura, Toshiaki Furuta, Hitoshi Okamoto

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)


The telencephalon shows the greatest degree of size variation in the vertebrate brain. Understanding the genetic cascade that regulates telencephalon growth is crucial to our understanding of how evolution of the normal human brain has supported such a variation in size. Here, we present a simple and quick approach to analyze this cascade that combines caged-mRNA technology and the use of antisense morpholino oligonucleotides in zebrafish embryos. Lhx2, a LIM-homeodomain protein, and Six3s (Six3b and Six3a), another homeodomain proteins, show very similar expression patterns early in forebrain development, and these are known to be involved in the growth of this part of the brain. The telencephalon of six3b and six3a double morphant (six3 morphant) embryos is markedly reduced in size due to impaired cellular proliferation. Head-specific overexpression of Lhx2 by photoactivation of a caged-lhx2 mRNA completely rescued this size reduction, whereas similar head-specific activation of Six3b could not rescue the knockdown effect of lhx2. In the forebrain of medaka embryos, Six3 facilitates cellular proliferation by sequestration of Geminin from Cdt1, a key component in the assembly of the prereplication complex. Our results suggest that Lhx2 may mediate an alternative or parallel pathway for control of cellular proliferation in the developing forebrain via Six3.

Original languageEnglish
Pages (from-to)456-468
Number of pages13
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 2005 Nov 15


  • Antisense morpholinos
  • Cell proliferation
  • Forebrain
  • Zebrafish
  • lhx2
  • mRNA caging
  • six3

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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