Otx dose-dependent integrated control of antero-posterior and dorso-ventral patterning of midbrain

Nat Neurosci. 2003 May;6(5):453-60. doi: 10.1038/nn1037.


Organizing centers emit signaling molecules that specify different neuronal cell types at precise positions along the anterior-posterior (A-P) and dorsal-ventral (D-V) axes of neural tube during development. Here we report that reduction in Otx proteins near the alar-basal plate boundary (ABB) of murine midbrain resulted in a dorsal shift of Shh expression, and reduction in Otx proteins at the midbrain-hindbrain boundary (MHB) resulted in an anterior expansion of the Fgf8 domain. Our data thus indicate that an Otx dose-dependent repressive effect coordinates proper positioning of Shh and Fgf8 expression. Furthermore, this control is effective for conferring proper cell identity in the floor-plate region of midbrain and does not require an Otx2-specific property. We propose that this mechanism may provide both A-P and D-V positional information to neuronal precursors located within the midbrain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning* / genetics
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Male
  • Mesencephalon / embryology*
  • Mesencephalon / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Otx Transcription Factors
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics


  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors