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J. Biol. Chem., Vol. 283, Issue 37, 25372-25380, September 12, 2008

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T-box Protein Tbx18 Interacts with the Paired Box Protein Pax3 in the Development of the Paraxial Mesoderm^*

Henner F. Farin, Ahmed Mansouri¹, Marianne Petry, and Andreas Kispert²

From the Institute for Molecular Biology, Medizinische Hochschule Hannover, OE5250, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany and the Department of Molecular Cell Biology, Max-Planck-Institute of Biophysical Chemistry, 37077 Göttingen, Germany

The compartmentalization of somites along their anterior-posterior axis is crucial to the segmental organization of the vertebral column. Anterior-posterior somite polarity is generated in the anterior presomitic mesoderm by Mesp2 and Delta/Notch signaling and is further maintained by two transcriptional regulators, Uncx4.1 and Tbx18, acting in the posterior and anterior somite compartment, respectively. Here, we report that the paired box transcription factor Pax3 cooperates with the T-box protein Tbx18 in maintaining anterior somite half identity. Our findings that both genes are co-expressed in the anterior presomitic mesoderm and in early somites, that Pax3 and Tbx18 proteins physically interact, and that the loss of Pax3 gene function enhances the vertebral defects (i.e. the gain of vertebral elements derived from posterior somite halves in Tbx18 mutant mice) suggests that the two proteins cooperatively regulate the gene expression program necessary for maintaining anterior-posterior somite polarity. Genetic interaction of Pax3 with Tbx18 and the closely related T-box gene Tbx15 was also observed in the development of the scapula blade, indicating an additional cooperative function for these genes in the paraxial mesoderm.

Received for publication, April 8, 2008 , and in revised form, June 27, 2008.

^* This work was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft (DFG)) and by the DFG-funded cluster of excellence "REBIRTH" (to A. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by the Dr. Helmut Storz Stiftung and the Max-Planck-Society.

² To whom correspondence should be addressed. Tel.: 49-511-5324017; Fax: 49-511-5324283; E-mail: kispert.andreas{at}mh-hannover.de.

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