Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain-hindbrain boundary organizer.
The transcription factor Otx2 is expressed throughout the anterior neuroectoderm and is required for the formation of all forebrain- and midbrain-derived structures. The molecular determinants that cooperate with Otx2 to subdivide its expression domain into distinct functional units are, however, poorly understood at present. We show here that the TALE-homeodomain protein Meis2 is expressed in the chick tectal anlage and is both necessary and sufficient for tectal development. Unlike known tectum-inducing genes, the ability of Meis2 to initiate tectal development does not involve the formation of a secondary midbrain-hindbrain boundary organizer, but instead requires direct interaction with Otx2. Using an Otx2-dependent reporter assay we demonstrate that Meis2 competes with the Groucho co-repressor Tle4 (Grg4) for binding to Otx2 and thereby restores Otx2 transcriptional activator function. Together, our data suggest a model in which the balance between a co-repressor and a co-activator, which compete for binding to Otx2 in the mesencephalic vesicle, provides spatial and temporal control over tectal development. Controlled formation of Meis2-containing higher order protein complexes might thus serve as a general mechanism to achieve subdivision of the anterior neuroectoderm into distinct functional units during embryogenesis.
Agoston
Zsuzsa
Z
Department of Neuroanatomy, Max-Planck Institute for Brain Research, Deutschordenstr. 46, Frankfurt, Germany.
Schulte
Dorothea
D
D000818:Animals; D030801:Animals, Genetically Modified; D001667:Binding, Competitive; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism*; D020897:Organizers, Embryonic / Q000196:embryology / Q000378:metabolism; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors