Abstract
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.
Highlights
The metameric organization of the vertebral column derives from the somites, segmentally repeated units in the paraxial mesoderm
Work from a variety of vertebrate model systems has shown that somite formation is governed by an oscillator known as the segmentation clock that operates in the presomitic mesoderm (PSM) [4, 5]
One of the clones identified by the yeast two-hybrid screen harbored a partial cDNA for Pax3, a member of the gene family encoding paired box transcription factors
Summary
The metameric organization of the vertebral column derives from the somites, segmentally repeated units in the paraxial mesoderm. Genetic evidence from both loss- and gain-of-function studies in the mouse suggest that this process is controlled by the combined action of a pair of transcription factors, the T-box (Tbx) protein Tbx18 and the paired type homeobox protein Uncx4.1, which are expressed in anterior and posterior somite halves, respectively [8, 9].
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