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首页> 外文期刊>Development >Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.
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Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.

机译:Wnt8在外侧中胚层前体中对于体内神经后继化是必需的。

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摘要

The dorsal ectoderm of the vertebrate gastrula was proposed by Nieuwkoop to be specified towards an anterior neural fate by an activation signal, with its subsequent regionalization along the anteroposterior (AP) axis regulated by a graded transforming activity, leading to a properly patterned forebrain, midbrain, hindbrain and spinal cord. The activation phase involves inhibition of BMP signals by dorsal antagonists, but the later caudalization process is much more poorly characterized. Explant and overexpression studies in chick, Xenopus, mouse and zebrafish implicate lateral/paraxial mesoderm in supplying the transforming influence, which is largely speculated to be a Wnt family member. We have analyzed the requirement for the specific ventrolaterally expressed Wnt8 ligand in the posteriorization of neural tissue in zebrafish wild-type and Nodal-deficient embryos (Antivin overexpressing or cyclops;squint double mutants), which show extensive AP brain patterning in the absence of dorsal mesoderm. In different genetic situations that vary the extent of mesodermal precursor formation, the presence of lateral wnt8-expressing cells correlates with the establishment of AP brain pattern. Cell tracing experiments show that the neuroectoderm of Nodal-deficient embryos undergoes a rapid anterior-to-posterior transformation in vivo during a short period at the end of the gastrula stage. Moreover, in both wild-type and Nodal-deficient embryos, inactivation of Wnt8 function by morpholino (MO(wnt8)) translational interference dose-dependently abrogates formation of spinal cord and posterior brain fates, without blocking ventrolateral mesoderm formation. MO(wnt8) also suppresses the forebrain deficiency in bozozok mutants, in which inactivation of a homeobox gene causes ectopic wnt8 expression. In addition, the bozozok forebrain reduction is suppressed in bozozok;squint;cyclops triple mutants, and is associated with reduced wnt8 expression, as seen in cyclops;squint mutants. Hence, whereas boz and Nodal signaling largely cooperate in gastrula organizer formation, they have opposing roles in regulating wnt8 expression and forebrain specification. Our findings provide strong support for a model of neural transformation in which a planar gastrula-stage Wnt8 signal, promoted by Nodal signaling and dorsally limited by Bozozok, acts on anterior neuroectoderm from the lateral mesoderm to produce the AP regional patterning of the CNS.
机译:Nieuwkoop提议将脊椎动物腹肌的背外胚层通过激活信号指定为朝向前神经命运,随后沿前后(AP)轴进行区域化,并通过渐变的转化活动进行调控,从而导致正确构图的前脑,中脑,后脑和脊髓。激活阶段涉及背侧拮抗剂对BMP信号的抑制,但是后期的氧化化过程的表征要差得多。在小鸡,爪蟾,小鼠和斑马鱼中的外植体和过表达研究表明,侧向/近轴中胚层提供了转化影响,这在很大程度上被认为是Wnt家族成员。我们已经分析了在斑马鱼野生型和节点缺失型胚胎(Antivin过表达或独眼巨人;斜视双突变体)的神经组织的后部化过程中特定腹侧表达的Wnt8配体的需求,这些胚胎在没有背侧的情况下显示出广泛的AP脑模式中胚层。在改变中胚层前体形成程度的不同遗传情况下,侧向表达wnt8的细胞的存在与AP脑模式的建立相关。细胞追踪实验表明,结节缺陷型胚胎的神经外胚层在下腹阶段的短时间内在体内经历了从前到后的快速转化。此外,在野生型和Nodal缺陷型胚胎中,吗啉代(MO(wnt8))的翻译干扰对Wnt8功能的失活均能剂量依赖性地消除脊髓和后脑的命运,而不会阻止腹侧中胚层的形成。 MO(wnt8)还抑制了bozozok突变体中的前脑缺陷,其中同源异型盒基因的失活导致异位wnt8表达。另外,如在独眼巨人斜视突变体中所见,在独生灵,斜视独眼巨人三联体突变体中,抑制了bozozok前脑的减少,并且与减少的wnt8表达有关。因此,尽管boz和Nodal信号在胃胚组织器的形成过程中起着很大的作用,但它们在调节wnt8表达和前脑指标方面却具有相反的作用。我们的发现为神经转换模型提供了有力的支持,在该模型中,由Nodal信号促进并受Bozozok背侧限制的平面胃tru期Wnt8信号作用于中胚层外侧中胚层,从而产生CNS的AP区域模式。

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