Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a000869. doi: 10.1101/cshperspect.a000869.
The sequential formation of somites along the anterior-posterior axis is under control of multiple signaling gradients involving the Wnt, FGF, and retinoic acid (RA) pathways. These pathways show graded distribution of signaling activity within the paraxial mesoderm of vertebrate embryos. Although Wnt and FGF signaling show highest activity in the posterior, unsegmented paraxial mesoderm (presomitic mesoderm [PSM]), RA signaling establishes a countergradient with the highest activity in the somites. The generation of these graded activities relies both on classical source-sink mechanisms (for RA signaling) and on an RNA decay mechanism (for FGF signaling). Numerous studies reveal the tight interconnection among Wnt, FGF, and RA signaling in controlling paraxial mesoderm differentiation and in defining the somite-forming unit. In particular, the relationship to a molecular oscillator acting in somite precursors in the PSM-called the segmentation clock-has been recently addressed. These studies indicate that high levels of Wnt and FGF signaling are required for the segmentation clock activity. Furthermore, we discuss how these signaling gradients act in a dose-dependent manner in the progenitors of the paraxial mesoderm, partly by regulating cell movements during gastrulation. Finally, links between the process of axial specification of vertebral segments and Hox gene expression are discussed.
沿前-后轴顺序形成体节受涉及 Wnt、FGF 和视黄酸 (RA) 途径的多个信号梯度的控制。这些途径在脊椎动物胚胎的轴旁中胚层中显示信号活性的梯度分布。尽管 Wnt 和 FGF 信号显示在后未分段的轴旁中胚层（前体节中胚层 [PSM]）中具有最高活性，但 RA 信号建立了一个与体节中最高活性的反梯度。这些梯度活性的产生既依赖于经典的源-汇机制（对于 RA 信号），也依赖于 RNA 降解机制（对于 FGF 信号）。许多研究揭示了 Wnt、FGF 和 RA 信号在控制轴旁中胚层分化和定义体节形成单位中的紧密相互联系。特别是，最近已经解决了在 PSM 中的体节前体中起作用的分子振荡器（称为体节时钟）与它们之间的关系。这些研究表明，高水平的 Wnt 和 FGF 信号对于体节时钟活性是必需的。此外，我们讨论了这些信号梯度如何以剂量依赖的方式在轴旁中胚层的祖细胞中发挥作用，部分通过调节原肠胚形成期间的细胞运动。最后，讨论了脊椎段的轴向指定过程与 Hox 基因表达之间的联系。
