OptoLRP6 Illuminates Wnt Signaling in Early Embryo Development
OptoLRP6 Illuminates Wnt Signaling in Early Embryo Development
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DOI：
10.1016/j.jmb.2021.167053
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发表时间：
2021-08-17
影响因子：
5.6
通讯作者：
Good, Matthew C.
中科院分区：
文献类型：
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作者：
Garabedian, Mikael, V;Good, Matthew C.
在早期发育过程中，细胞命运的决定和组织的组织需要细胞间信号的精确时空协调。在后生动物中，无论是成体干细胞生境还是早期胚胎，都需要使用整个组织中精确的信号分子梯度进行持续的细胞-细胞交流，通过复杂的、多组分的信号传递路径传递位置和细胞命运信息。1这样的信息通过细胞外配体(如Wnt)远距离传递，以刺激受体激活并促进下游基因表达程序。WNT信号是一个古老而保守的信号转导途径，在早期胚胎发育中起着许多核心作用。2在两栖类胚胎的囊胚期，Wnt信号通过FrizzledFRZ和LRP5/6共受体负责稳定背侧细胞中的b-catenin，并建立Spemann组织者，从而促进背腹轴的形成。3进一步的研究表明，规范的Wnt信号机制促进了其他门中类似的背部组织者的形成，这表明即使不是所有的脊椎动物，也是大多数脊椎动物的背部组织者。4之后，在原肠形成过程中，Wnt信号对后部细胞的命运起作用。在不适当的组织中，如腹侧细胞，激活规范的Wnt途径或稳定b-catenin，足以在两栖类胚胎中形成次生轴。5-8
Cell fate determination and tissue organization during early development requires precise spatiotemporal coordination of cell-to-cell signaling. In metazoans, both adult stem cell niches and early embryos require continuous cell–cell communication using precise gradients of signaling molecules throughout the tissue, conveying positional and cell fate information through complex, multicomponent signal relay pathways. 1 Such information is transmitted across large distances via extracellular ligands, such as Wnt, to stimulate receptor activation and promote downstream gene expression programs. Wnt signaling is an ancient and conserved signal transduction pathway with a number of central roles in early embryonic development. 2 In the blastula stage of amphibian embryos, Wnt signaling through Frizzled (Frz) and the LRP5/6 co-receptors is responsible for stabilizing b-catenin in dorsal cells and for establishing the Spemann Organizer, thereby promoting the formation of the dorsoventral axis. 3 Further studies have shown that canonical Wnt signaling mechanisms promote the formation of similar dorsal organizer in other phyla, suggesting conservation in most, if not all, vertebrate species. 4 Later, during gastrulation, Wnt signaling contributes to posterior cell fates. Activation of the canonical Wnt pathway or stabilization of b-catenin in inappropriate tissues, such as in ventral cells, is sufficient to form a secondary axis in amphibian embryos. 5–8