title: Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors.
abstract: One of the earliest organizational decisions in the development of the vertebrate brain is the division of the neural plate into Otx2-positive anterior and Gbx2-positive posterior territories. At the junction of these two expression domains, a local signaling center is formed, known as the midbrain-hindbrain boundary (MHB). This tissue coordinates or "organizes" the development of neighboring brain structures, such as the midbrain and cerebellum. Correct positioning of the MHB is thought to depend on mutual repression involving these two homeobox genes. Using a cell culture colocalization assay and coimmunoprecipitation experiments, we show that engrailed homology region 1 (eh1)-like motifs of both transcription factors physically interact with the WD40 domain of Groucho/Tle corepressor proteins. In addition, heat shock-induced expression of wild-type and mutant Otx2 and Gbx2 in medaka embryos demonstrates that Groucho is required for the repression of Otx2 by Gbx2. On the other hand, the repressive functions of Otx2 on Gbx2 do not appear to be dependent on corepressor interaction. Interestingly, the association of Groucho with Otx2 is also required for the repression of Fgf8 in the MHB. Therefore Groucho/Tle family members appear to regulate key aspects in the MHB development of the vertebrate brain.
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Heimbucher
authors.forename: Christina
authors.initials: C
authors.lastname: Murko
authors.forename: Baubak
authors.initials: B
authors.lastname: Bajoghli
authors.forename: Narges
authors.initials: N
authors.lastname: Aghaallaei
authors.forename: Anja
authors.initials: A
authors.lastname: Huber
authors.forename: Ronald
authors.initials: R
authors.lastname: Stebegg
authors.forename: Dirk
authors.initials: D
authors.lastname: Eberhard
authors.forename: Maria
authors.initials: M
authors.lastname: Fink
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.forename: Thomas
authors.initials: T
authors.lastname: Czerny
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D009990:Oryzias; D051857:Otx Transcription Factors / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C084958:GBX2 protein, human; C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D012097:Repressor Proteins; C465817:TLE4 protein, human; C434949:Tle4 protein, mouse