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Molecular and Cellular Biology, January 2007, p. 340-351, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00811-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Gbx2 and Otx2 Interact with the WD40 Domain of Groucho/Tle Corepressors{triangledown} ,{ddagger}

Thomas Heimbucher,1 Christina Murko,1 Baubak Bajoghli,1 Narges Aghaallaei,1 Anja Huber,1 Ronald Stebegg,1 Dirk Eberhard,1,{dagger} Maria Fink,1 Antonio Simeone,2,3,4 and Thomas Czerny1*

Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria,1 CEINGE Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Naples, Italy,2 MRC Centre for Develeopmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London Bridge, London SE1 1UL, United Kingdom,3 Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Via P. Castellino 111, 80131 Naples, Italy4

Received 8 May 2006/ Returned for modification 18 July 2006/ Accepted 27 September 2006

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.

* Corresponding author. Mailing address: Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria. Phone: 43 1 25077 5639. Fax: 43 1 25077 5693. E-mail: thomas.czerny{at}vu-wien.ac.at.

{triangledown} Published ahead of print on 23 October 2006.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} Present address: Cellzome AG, Meyerhofstrasse 1 69117 Heidelberg, Germany.

Molecular and Cellular Biology, January 2007, p. 340-351, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00811-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Agoston, Z., Schulte, D. (2009). 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. Development 136: 3311-3322 [Abstract] [Full Text]  
  • Larder, R., Mellon, P. L. (2009). Otx2 Induction of the Gonadotropin-releasing Hormone Promoter Is Modulated by Direct Interactions with Grg Co-repressors. J. Biol. Chem. 284: 16966-16978 [Abstract] [Full Text]  


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