Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction

Gene Expr Patterns. 2005 Dec;6(1):110-8. doi: 10.1016/j.modgep.2005.04.010. Epub 2005 Jul 18.


The Drosophila eyeless gene plays a central role in fly eye development and controls a subordinate regulatory network consisting of the so, eya and dac genes. All three genes have highly conserved mammalian homologs, suggesting possible conservation of this eye forming regulatory network. sine oculis (so) belongs to the so/Six gene family, and Six3 is prominently expressed in the developing mammalian eye. Eya1 and Dach1 are mammalian homologs of eya and dac, respectively, and although neither Eya1 nor Dach1 knockout mice express prenatal eye defects, possibilities exist for postnatal ocular phenotypes or for functional redundancy between related family members. To examine whether expression relationships analogous to those between ey, so, eya and dac exist in early mammalian oculogenesis, we investigated Pax6, Six3, Eya1 and Dach1 protein expression in murine lens and nasal placode development. Six3 expression in the pre-placode lens ectoderm is initially Pax6-independent, but subsequently both its expression and nuclear localization become Pax6-dependent. Six3, Dach1 and Eya1 nasal expression in pre-placode ectoderm are also initially Pax6-independent, but thereafter become Pax6-dependent. Pax6, Six3, Dach1 and Eya1 are all co-expressed in the developing ciliary marginal zone, a source of retinal stem cells in some vertebrates. An in vitro protein-protein interaction is detected between Six3 and Eya1. Collectively, these findings suggest that the Pax-Eya-Six-Dach network is at best only partly conserved during lens and nasal placode development. However, the findings do not rule out the possibility that such a regulatory network acts at later stages of oculogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Eye Proteins / analysis
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lens, Crystalline / chemistry
  • Lens, Crystalline / embryology*
  • Lens, Crystalline / metabolism
  • Mice
  • Mice, Knockout
  • Nasal Mucosa / metabolism
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nose / chemistry
  • Nose / embryology*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / analysis
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*


  • Dach1 protein, mouse
  • Eye Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Sine oculis homeobox homolog 3 protein
  • Eya1 protein, mouse
  • Protein Tyrosine Phosphatases