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Open Access Highly Accessed Research article

Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development

Zsuzsa Agoston124, Naixin Li35, Anja Haslinger26, Andrea Wizenmann37 and Dorothea Schulte12*

Author Affiliations

1 Institute of Neurology (Edinger Institute), J. W. Goethe University Medical School, Heinrich Hoffmannstr. 7, 50628 Frankfurt, Germany

2 Max Planck Institute for Brain Research, Deutschordenstr. 46, 50628 Frankfurt, Germany

3 JRG Developmental Neurobiology, Biocenter, Julius Maximilians University, Am Hubland, 97074 Würzburg, Germany

4 Department of Pharmacology, Howard Hughes Medical Institute, and the Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA98109, USA

5 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China

6 Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

7 Institute of Anatomy, Experimental Embryology, Eberhard Karls University, Tübingen, Germany

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BMC Developmental Biology 2012, 12:10  doi:10.1186/1471-213X-12-10

Published: 5 March 2012

Abstract

Background

During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.

Results

Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage.

Conclusion

The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.