Zákány J, Gérard M, Favier B, Duboule D
Department of Zoology and Animal Biology, University of Geneva, Sciences III, Switzerland.
EMBO J. 1997 Jul 16;16(14):4393-402. doi: 10.1093/emboj/16.14.4393.
A phylogenetically conserved transcriptional enhancer necessary for the activation of Hoxd-11 was deleted from the HoxD complex of mice by targeted mutagenesis. While genetic and expression analyses demonstrated the role of this regulatory element in the activation of Hoxd-11 during early somitogenesis, the function of this gene in developing limbs and the urogenital system was not affected, suggesting that Hox transcriptional controls are different in different axial structures. In the trunk of mutant embryos, transcriptional activation of Hoxd-11 and Hoxd-10 was severely delayed, but subsequently resumed with appropriate spatial distributions. The resulting caudal transposition of the sacrum indicates that proper vertebral specification requires a precise temporal control of Hox gene expression, in addition to spatial regulation. A slight time delay in expression (transcriptional heterochrony) cannot be compensated for at a later developmental stage, eventually leading to morphological alterations.
通过靶向诱变从小鼠的HoxD复合体中删除了激活Hoxd - 11所必需的系统发育保守转录增强子。虽然遗传和表达分析证明了该调控元件在早期体节形成过程中对Hoxd - 11激活的作用，但该基因在发育中的肢体和泌尿生殖系统中的功能并未受到影响，这表明Hox转录调控在不同的轴向结构中有所不同。在突变胚胎的躯干中，Hoxd - 11和Hoxd - 10的转录激活严重延迟，但随后以适当的空间分布恢复。由此导致的骶骨尾侧移位表明，除了空间调控外，正确的椎体特化还需要对Hox基因表达进行精确的时间控制。表达上的轻微时间延迟（转录异时性）在发育后期无法得到补偿，最终导致形态改变。
