Hoppler S, Moon R T
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle 98195, USA.
Mech Dev. 1998 Feb;71(1-2):119-29. doi: 10.1016/s0925-4773(98)00004-5.
Establishment of the dorsoventral axis is central to animal embryonic organization. In Xenopus two different classes of signaling molecules function in the dorsoventral patterning of the mesoderm. Both the TGF-beta-related products of the BMP-2 and BMP-4 genes and the Wnt molecule encoded by Xenopus Wnt-8 specify ventral fate and appear to inhibit dorsal mesodermal development. The similar functions of these molecularly very different classes of signaling molecules prompted us to study their mutual regulation and to closely compare their roles in mesoderm patterning. We find that Wnt-8 and BMP-4 are indistinguishable in their abilities to induce expression of ventral genes. Although BMP-2/-4 signaling regulates Wnt-8 expression, these genes do not function in a linear pathway because Wnt-8 overexpression cannot compensate for an inhibition of BMP-2/-4 function, but rather BMP-4 overexpression rescues ventral gene expression in embryos with inhibited Wnt-8 function. We further find that Wnt-8 and BMP-2/-4 differ in their abilities to regulate dorsal gene expression. While BMP-4 appears to generally inhibit the expression of dorsal genes, XenopusWnt-8 only inhibits the expression of the notochord marker Xnot. Whereas the inhibitory effect of BMP-2/-4 localizes dorsal mesodermal fate, our results suggest that Xenopus Wnt-8 functions in the further patterning of the dorsal mesoderm into the most dorsal sector from which the notochord develops and the dorsolateral sector from where the somites differentiate.
背腹轴的建立是动物胚胎组织形成的核心。在非洲爪蟾中，两类不同的信号分子在中胚层的背腹模式形成中发挥作用。BMP - 2和BMP - 4基因的TGF - β相关产物以及非洲爪蟾Wnt - 8编码的Wnt分子都决定腹侧命运，并且似乎抑制背侧中胚层的发育。这些分子结构差异很大的信号分子具有相似的功能，这促使我们研究它们之间的相互调节，并仔细比较它们在中胚层模式形成中的作用。我们发现，Wnt - 8和BMP - 4在诱导腹侧基因表达的能力上没有区别。虽然BMP - 2/-4信号调节Wnt - 8的表达，但这些基因并非以线性途径发挥作用，因为Wnt - 8的过表达不能补偿BMP - 2/-4功能的抑制，相反，BMP - 4的过表达能挽救Wnt - 8功能受抑制胚胎中的腹侧基因表达。我们进一步发现，Wnt - 8和BMP - 2/-4在调节背侧基因表达的能力上存在差异。虽然BMP - 4似乎普遍抑制背侧基因的表达，但非洲爪蟾Wnt - 8仅抑制脊索标记物Xnot的表达。虽然BMP - 2/-4的抑制作用确定了背侧中胚层的命运，但我们的结果表明，非洲爪蟾Wnt - 8在将背侧中胚层进一步模式化为脊索发育的最背侧区域和体节分化的背外侧区域中发挥作用。
