DELETION OF A HOXD ENHANCER INDUCES TRANSCRIPTIONAL HETEROCHRONY LEADING TO TRANSPOSITION OF THE SACRUM

A phylogenetically conserved transcriptional enhancer necessary for th e activation of Hoxd-11 was deleted from the HoxD complex of mice by t argeted mutagenesis, While genetic and expression analyses demonstrate d the role of this regulatory element in the activation of Hoxd-11 dur ing early somitogenesis, the function of this gene in developing limbs and the urogenital system was not affected, suggesting that Hox trans criptional controls are different in different axial structures, In th e trunk of mutant embryos, transcriptional activation of Hoxd-11 and H oxd-10 was severely delayed, but subsequently resumed with appropriate spatial distributions. The resulting caudal transposition of the sacr um indicates that proper vertebral specification requires a precise te mporal control of Hox gene expression, in addition to spatial regulati on, A slight time delay in expression (transcriptional heterochrony) c annot be compensated for at a later developmental stage, eventually le ading to morphological alterations.