Peres João N, McNulty Claire L, Durston Anthony J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.
Mech Dev. 2006 Apr;123(4):321-33. doi: 10.1016/j.mod.2006.03.001. Epub 2006 Apr 27.
In vertebrates, the paraxial mesoderm already exhibits a complex Hox gene pattern by the time that segmentation occurs and somites are formed. The anterior boundaries of the Hox genes are always maintained at the same somite number, suggesting coordination between somite formation and Hox expression. To study this interaction, we used morpholinos to knockdown either the somitogenesis gene X-Delta-2 or the complete Hox paralogous group 1 (PG1) in Xenopus laevis. When X-Delta-2 is knocked down, Hox genes from different paralogous groups are downregulated from the beginning of their expression at gastrula stages. This effect is not via the canonical Notch pathway, as it is independent of the Notch effector Su(H). We also reveal for the first time a clear role for Hox genes in somitogenesis, as loss of PG1 gene function results in the perturbation of somite formation and downregulation of the X-Delta-2 expression in the PSM. This effect on X-Delta-2 expression is also observed during neurula stages, before the somites are formed. These results show that somitogenesis and patterning of the anteroposterior axis are closely linked via a feedback loop involving Hox genes and X-Delta-2, suggesting the existence of a coordination mechanism between somite formation and anteroposterior patterning. Such a mechanism is likely to be functional during gastrulation, before the formation of the first pair of somites, as suggested by the early X-Delta-2 regulation of the Hox genes.
在脊椎动物中，当发生体节分割并形成体节时，轴旁中胚层已经呈现出复杂的Hox基因模式。Hox基因的前边界总是维持在相同的体节数量，这表明体节形成与Hox基因表达之间存在协调。为了研究这种相互作用，我们使用吗啉代寡核苷酸敲低非洲爪蟾中的体节发生基因X-Delta-2或完整的Hox同源基因群1（PG1）。当X-Delta-2被敲低时，来自不同同源基因群的Hox基因从原肠胚阶段开始表达时就被下调。这种效应不是通过经典的Notch信号通路，因为它独立于Notch效应因子Su(H)。我们还首次揭示了Hox基因在体节发生中的明确作用，因为PG1基因功能的丧失导致体节形成受到干扰以及PSM中X-Delta-2表达下调。在神经胚阶段，即在体节形成之前，也观察到了对X-Delta-2表达的这种影响。这些结果表明体节发生和前后轴模式通过涉及Hox基因和X-Delta-2的反馈环紧密相连，这表明在体节形成和前后模式之间存在一种协调机制。正如Hox基因早期的X-Delta-2调控所表明的那样，这种机制可能在原肠胚形成期间，即在第一对体节形成之前就发挥作用。
