Essential and opposing roles of zebrafish β-catenins in the formation of dorsal axial structures and neurectoderm
Essential and opposing roles of zebrafish β-catenins in the formation of dorsal axial structures and neurectoderm
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DOI：
10.1242/dev.02295
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发表时间：
2006-04-01
期刊：
影响因子：
4.6
通讯作者：
Weinberg, ES
中科院分区：
文献类型：
--
作者：
Bellipanni, G;Varga, MT;Weinberg, ES
在非洲爪蟾中，Wnt信号及其转录效应子β-连环蛋白是背轴结构发育所必需的。在斑马鱼中，以前的功能丧失研究没有确定β-连环蛋白在背轴形成中的重要作用，但母亲效应突变ichabod破坏了背核中β-连环蛋白的积累，并导致背前衍生物的减少。我们已经确定并表征了第二个斑马鱼β-连环蛋白基因，β-连环蛋白-2，位于与先前研究的β-连环蛋白-1不同的连锁群上，但靠近LG 19上的ichabod突变。虽然ichabod突变不会在功能上改变β-连环蛋白-2阅读框架，但与野生型胚胎相比，ichabod胚胎中母体β-连环蛋白-2转录物的水平显著降低，但β-连环蛋白-1转录物的水平不降低。通过注射特异于该基因（MO 2）的吗啉代反义寡核苷酸（MO）降低野生型胚胎中的β-连环蛋白-2功能导致与在ichabod胚胎中观察到的相同的腹侧化表型，并且向ichabod胚胎施用MO 2增加腹侧化的程度。相反，针对β-连环蛋白-1（MO 1）的MO对野生型胚胎没有腹侧化作用。因此，β-连环蛋白-2是组织者形成所特别需要的，并且该功能显然是母体所需要的，因为ichabod突变导致该基因的母体转录减少和早期胚胎中β-连环蛋白-2蛋白水平降低。当两个β-连环蛋白基因都被抑制时，β-连环蛋白在抑制神经外胚层形成中的冗余作用被揭示。在野生型胚胎中使用MO 1和MO 2的组合，或通过在ichabod胚胎中单独注射MO 1，我们以明显适当的前后模式获得了广泛的神经标志物的表达。我们提出，早期，背促进功能的β-连环蛋白-2是必不可少的，以抵消后来，背和neurectoderm-repressing功能，这是共享的β-连环蛋白基因。
In Xenopus, Wnt signals and their transcriptional effector beta-catenin are required for the development of dorsal axial structures. In zebra fish, previous loss-of-function studies have not identified an essential role for beta-catenin in dorsal axis formation, but the maternal-effect mutation ichabod disrupts beta-catenin accumulation in dorsal nuclei and leads to a reduction of dorsoanterior derivatives. We have identified and characterized a second zebrafish beta-catenin gene, beta-catenin-2, located on a different linkage group from the previously studied beta-catenin-1, but situated close to the ichabod mutation on LG19. Although the ichabod mutation does not functionally alter the beta-catenin-2 reading frame, the level of maternal beta-catenin-2, but not beta-catenin-1, transcript is substantially lower in ichabod, compared with wild-type, embryos. Reduction of beta-catenin-2 function in wild- type embryos by injection of morpholino antisense oligonucleotides (MOs) specific for this gene (MO2) results in the same ventralized phenotypes as seen in ichabod embryos, and administration of MO2 to ichabod embryos increases the extent of ventralization. MOs directed against beta-catenin-1 (MO1), by contrast, had no ventralizing effect on wild- type embryos. beta-catenin-2 is thus specifically required for organizer formation and this function is apparently required maternally, because the ichabod mutation causes a reduction in maternal transcription of the gene and a reduced level of beta-catenin-2 protein in the early embryo. A redundant role of beta-catenins in suppressing formation of neurectoderm is revealed when both beta-catenin genes are inhibited. Using a combination of MO1 and MO2 in wild-type embryos, or by injecting solely MO1 in ichabod embryos, we obtain expression of a wide spectrum of neural markers in apparently appropriate anteroposterior pattern. We propose that the early, dorsal-promoting function of beta-catenin-2 is essential to counteract a later, dorsal-and neurectoderm-repressing function that is shared by both beta-catenin genes.