Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.
Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.
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发表时间：
2001-09
期刊：
影响因子：
4.6
通讯作者：
Caroline E. Erter;T. Wilm;Nathan Basler;C. V. Wright;L. Solnica-Krezel
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作者：
Caroline E. Erter;T. Wilm;Nathan Basler;C. V. Wright;L. Solnica-Krezel
Nieuwkoop提出了脊椎动物胃的背侧外胚层，通过激活信号指定向前神经命运，其随后沿着前后轴（AP）轴的区域化，该轴由分级的转化活性调节，导致适当的前脑，中脑，导致了良好，后脑和脊髓。激活阶段涉及背侧拮抗剂抑制BMP信号，但后来的尾含量过程的表征较差。鸡，爪蟾，小鼠和斑马鱼中的外植物和过表达研究暗示了横向/近去中胚层提供转化影响，这在很大程度上被推测为Wnt家族成员。我们已经分析了特异性腹侧表达的Wnt8配体在斑马鱼野生型和节点缺陷型胚胎（抗抗素过表达或cyclops; Squint Double Mutants）中的神经组织中的特异性Wnt8配体的需求中胚层。在改变中胚层前体形成程度的不同遗传情况下，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，淋巴结缺陷的胚胎的神经外胚层在胃阶段结束时的短时间内在体内经历了快速的前到后者转化。此外，在野生型和淋巴结缺陷的胚胎中，莫菲利诺（MO（Wnt8））转化干扰剂量依赖性地依赖性地消除了脊髓和后脑命运的形成，而不会阻止腹侧中外侧中胚层的形成。 MO（Wnt8）还抑制了Bozozok突变体的前脑缺乏，其中同源基因的失活会导致异位WNT8表达。另外，Bozozok前脑还原抑制了Bozozok; sindint; Cyclops三重突变体，并与wnt8表达降低相关，如独眼巨人所见； quint斜突变体。因此，尽管Boz和Nodal信号在胃组织者形成中基本上合作，但它们在调节Wnt8表达和前脑规范方面具有相反的作用。我们的发现为神经转化模型提供了强有力的支持，在这种模型中，该模型由淋巴结信号传导促进并受到Bozozok的背面限制的平面胃阶段WNT8信号，作用于侧向中码的前神经电型师，从而产生CNS的AP型区域模式。
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.