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Wbp2nl has a developmental role in establishing neural and non-neural ectodermal fates

机译:Wbp2nl在建立神经和非神经外胚层命运方面具有发展作用

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摘要

In many animals, maternally synthesized mRNAs are critical for primary germ layer formation. In Xenopus, several maternal mRNAs are enriched in the animal blastomere progenitors of the embryonic ectoderm. We previously identified one of these, WW-domain binding protein 2 N-terminal like (wbp2nl), that others previously characterized as a sperm protein (PAWP) that promotes meiotic resumption. Herein we demonstrate that it has an additional developmental role in regionalizing the embryonic ectoderm. Knock-down of Wbp2nl in the dorsal ectoderm reduced cranial placode and neural crest gene expression domains and expanded neural plate domains; knock-down in ventral ectoderm reduced epidermal gene expression. Conversely, increasing levels of Wbp2nl in the neural plate induced ectopic epidermal and neural crest gene expression and repressed many neural plate and cranial placode genes. The effects in the neural plate appear to be mediated, at least in part, by down-regulating chd, a BMP antagonist. Because the cellular function of Wbp2nl is not known, we mutated several predicted motifs. Expressing mutated proteins in embryos showed that a putative phosphorylation site at Thr45 and an α-helix in the PH-G domain are required to ectopically induce epidermal and neural crest genes in the neural plate. An intact YAP-binding motif also is required for ectopic epidermal gene expression as well as for down-regulating chd. This work reveals novel developmental roles for a cytoplasmic protein that promotes epidermal and neural crest formation at the expense of neural ectoderm.
机译:在许多动物中,母体合成的mRNA对于初级细菌层的形成至关重要。在非洲爪蟾中,几种母体mRNA富集于胚胎外胚层的动物卵裂球祖细胞中。我们先前确定了其中之一,WW域结合蛋白2 N末端类似(wbp2nl),其他人先前将其表征为促进减数分裂恢复的精子蛋白(PAWP)。在本文中,我们证明了它在胚胎外胚层区域化中具有额外的发展作用。击倒Wbp2nl在背外胚层中减少了颅骨斑和神经c基因表达域,并扩展了神经板域。击倒腹外胚层减少表皮基因表达。相反,在神经板中增加Wbp2nl的水平会诱导异位表皮和神经c基因表达,并抑制许多神经板和颅底基因。神经板中的作用似乎至少部分是通过下调BMP拮抗剂chd介导的。由于Wbp2nl的细胞功能未知,我们突变了几个预测的基序。在胚胎中表达突变的蛋白质表明,在异位诱导神经板中的表皮和神经c基因需要Thr45的假定磷酸化位点和PH-G域中的α-螺旋。异位表皮基因表达以及下调chd也需要完整的YAP结合基序。这项工作揭示了胞质蛋白的新发展作用,该蛋白促进神经外胚层的生长促进表皮和神经expense的形成。

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