T-box protein Tbx18 interacts with the paired box protein Pax3 in the development of the paraxial mesoderm.
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.
Farin
Henner F
HF
Institute for Molecular Biology, Medizinische Hochschule Hannover, OE5250, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany and the.
Mansouri
Ahmed
A
Department of Molecular Cell Biology, Max-Planck-Institute of Biophysical Chemistry, 37077 Göttingen, Germany.
Petry
Marianne
M
Institute for Molecular Biology, Medizinische Hochschule Hannover, OE5250, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany and the.
Kispert
Andreas
A
Institute for Molecular Biology, Medizinische Hochschule Hannover, OE5250, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany and the. Electronic address: kispert.andreas@mh-hannover.de.
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D012540:Scapula / Q000196:embryology; D019170:Somites / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse; D014157:Transcription Factors; C068686:Pax3 protein, mouse