Bmp inhibition is necessary for post-gastrulation patterning and morphogenesis of the zebrafish tailbud.

Bmp inhibition is necessary for post-gastrulation patterning and morphogenesis of the zebrafish tailbud.
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DOI:
10.1016/j.ydbio.2009.02.016
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发表时间:
2009-05-01
影响因子:
2.7
通讯作者:
Kimelman, David
Kimelman, David
中科院分区:
生物学3区
文献类型:
--
作者:
Row, Richard H.;Kimelman, David

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Wnt和Bmp信号通路之间复杂的相互作用利用分泌蛋白配体和抑制剂网络来模式原肠胚脊椎动物胚胎。虽然许多这些蛋白在原肠期后表达,但由于早期扰动的影响,它们后来的作用通常仍不清楚。我们发现Bmp信号在斑马鱼胚胎的躯体发生过程中持续存在,在胚胎后端中胚层祖细胞区的一小块区域具有高活性。为了验证在尾芽前表达Bmp抑制剂对抑制Bmp信号很重要的假设,我们生产了一个新的斑马鱼转基因系,允许Bmp信号的时间细胞自主激活,从而绕过Bmp抑制剂的影响。在体细胞发生过程中,Bmp信号的异位激活导致尾芽严重缺陷,包括形态发生和基因表达的改变。我们表明这些缺陷是由于尾芽上的非自主效应,并提供证据表明尾芽缺陷是由Wnt信号的改变引起的。我们提出了一个模型,在该模型中,后表达的Bmp抑制剂在体细胞发生过程中抑制尾芽中的Bmp信号传导,从而允许Wnt抑制剂在体细胞前中胚层中正常表达,从而限制尾芽中典型和非典型Wnt信号传导的水平。
Intricate interactions between the Wnt and Bmp signaling pathways pattern the gastrulating vertebrate embryo using a network of secreted protein ligands and inhibitors. While many of these proteins are expressed post-gastrula, their later roles have typically remained unclear, obscured by the effects of early perturbation. We find that Bmp signaling continues during somitogenesis in zebrafish embryos, with high activity in a small region of the mesodermal progenitor zone at the posterior end of the embryo. To test the hypothesis that Bmp inhibitors expressed just anterior to the tailbud are important to restrain Bmp signaling we produced a new zebrafish transgenic line, allowing temporal cell-autonomous activation of Bmp signaling and thereby bypassing the effects of the Bmp inhibitors. Ectopic activation of Bmp signaling during somitogenesis results in severe defects in the tailbud, including altered morphogenesis and gene expression. We show that these defects are due to non-autonomous effects on the tailbud, and present evidence that the tailbud defects are caused by alterations in Wnt signaling. We present a model in which the posteriorly expressed Bmp inhibitors function during somitogenesis to constrain Bmp signaling in the tailbud in order to allow normal expression of Wnt inhibitors in the presomitic mesoderm, which in turn constrain the levels of canonical and non-canonical Wnt signaling in the tailbud.
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