The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm
The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm
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DOI：
10.1242/dev.00400
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发表时间：
2003-05-01
期刊：
影响因子：
4.6
通讯作者：
Talbot, WS
中科院分区：
文献类型：
--
作者：
Dougan, ST;Warga, RM;Talbot, WS
结节信号是转化生长因子β超家族分泌因子的一个亚类，在脊椎动物胚胎中诱导中胚层和内胚层的形成。我们通过使用两个斑马鱼结节相关基因的突变，斜视和独眼，研究了可能的背腹和动植物模式对结节信号的作用，以从遗传上操纵结节活动的水平和时间。斜视突变体在胚泡发育后期缺乏背侧中胚层基因的表达，而在SQT(-/-)、Cyc(+/+)和SQT(-/-)突变体中的命运定位和基因表达研究表明，一些背侧边缘细胞不适当地形成后脑和脊髓，而不是背侧中内胚层衍生物。对腹外侧部中胚层的影响较轻，但对内胚层的影响较小。是减少的，肌肉前体比野生型更接近边缘。我们的结果支持Nodal信号在沿着动植物轴线形成中胚层的模式中所起的作用，并表明背侧和腹外侧中胚层需要不同水平的斜视和独眼眼球功能。在SQT(-/-)；Cyc(+/-)或SQT(-/-)、Cyc(+/+)胚胎中，背侧边缘细胞没有向更外侧的命运转化，这与结节信号在中胚层背腹模式中的分级作用相矛盾。这些细胞中独眼巨人基因的不同调控导致了这些细胞对结节相关基因功能的不同要求。单环蛋白的背侧表达需要依赖于结节的自身调节，而其他因素则诱导腹侧细胞中单环蛋白的表达。此外，斜视突变体和独眼突变体背侧中胚层诱导的不同时间表明，背侧边缘细胞可以在从中期囊胚到中期原肠胚的各个阶段对Nodal信号做出反应。
Nodal signals, a subclass of the TGFbeta superfamily of secreted factors, induce formation of mesoderm and endoderm in vertebrate embryos. We have examined the possible dorsoventral and animal-vegetal patterning roles for Nodal signals by using mutations in two zebrafish nodal-related genes, squint and cyclops, to manipulate genetically the levels and timing of Nodal activity. squint mutants lack dorsal mesendodermal gene expression at the late blastula stage, and fate mapping and gene expression studies in sqt(-/-), cyc(+/+) and sqt(-/-); cyc(+/-) mutants show that some dorsal marginal cells inappropriately form hindbrain and spinal cord instead of dorsal mesendodermal derivatives. The effects on ventrolateral mesendoderm are less severe, although the endoderm. is reduced and muscle precursors are located nearer to the margin than in wild type. Our results support a role for Nodal signals in patterning the mesendoderm along the animal-vegetal axis and indicate that dorsal and ventrolateral mesoderm require different levels of squint and cyclops function. Dorsal marginal cells were not transformed toward more lateral fates in either sqt(-/-); cyc(+/-) or sqt(-/-), cyc(+/+) embryos, arguing against a role for the graded action of Nodal signals in dorsoventral patterning of the mesendoderm. Differential regulation of the cyclops gene in these cells contributes to the different requirements for nodal-related gene function in these cells. Dorsal expression of cyclops requires Nodal-dependent autoregulation, whereas other factors induce cyclops expression in ventrolateral cells. In addition, the differential timing of dorsal mesendoderm induction in squint and cyclops mutants suggests that dorsal marginal cells can respond to Nodal signals at stages ranging from the mid-blastula through the mid-gastrula.