Neuroepithelial co-expression of Gbx2 and Otx2 precedes Fgf8 expression in the isthmic organizer

Mech Dev. 2001 Mar;101(1-2):111-8. doi: 10.1016/s0925-4773(00)00567-0.


The most studied secondary neural organizer is the isthmic organizer, which is localized at the mid-hindbrain transition of the neural tube and controls the anterior hindbrain and midbrain regionalization. Otx2 and Gbx2 expressions are fundamental for positioning the organizer and the establishment of molecular interactions that induce Fgf8. We present here evidences demonstrating that Otx2 and Gbx2 have an overlapping expression in the isthmic region. This area is the transversal domain where expression of Fgf8 is induced. The Fgf8 protein produced in the isthmus stabilizes and up-regulates Gbx2 expression, which, in turn, down-regulates Otx2 expression. The inductive effect of the Gbx2/Otx2 limit keeps Fgf8 expression stable and thus maintains its positive role in the expression of Pax2, En1,2 and Wnt1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / embryology*
  • Brain / metabolism
  • Chick Embryo
  • Culture Techniques
  • DNA-Binding Proteins / biosynthesis
  • Down-Regulation
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / biosynthesis*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / biosynthesis*
  • In Situ Hybridization
  • Mice
  • Models, Biological
  • Nerve Tissue Proteins / biosynthesis*
  • Otx Transcription Factors
  • PAX2 Transcription Factor
  • Proto-Oncogene Proteins / biosynthesis
  • Time Factors
  • Trans-Activators / biosynthesis*
  • Transcription Factors / biosynthesis
  • Up-Regulation
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*


  • DNA-Binding Proteins
  • EN1 protein, human
  • En1 protein, mouse
  • Fgf8 protein, mouse
  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins
  • gbx2 protein, zebrafish
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors