Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity
Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity
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DOI：
10.1016/j.ydbio.2006.07.002
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发表时间：
2006-10-15
影响因子：
2.7
通讯作者：
Thisse, Christine
中科院分区：
文献类型：
--
作者：
Dal-Pra, Sophie;Fuerthauer, Maximilian;Thisse, Christine
在非洲爪蟾中，背腹（D/V）轴被认为是由骨形态发生蛋白（Bmp）活性所指定的，该活性是通过与拮抗剂如头蛋白、脊索蛋白和卵泡抑素相互作用而产生的。我们在这里报告，通过noggin 1（nog 1）的失活，这个基因本身并不是建立D/V模式所必需的。然而，在囊胚阶段，nog 1的失活强烈放大了脊索蛋白（chd）表型，揭示了这两个基因在D/V轴形成中的冗余功能。大量的背侧组织留在双nog 1-chd morphant表明，其他抗BMP因子可能图案的D/V轴。我们分离出两个潜在的候选基因，卵泡抑素样（fstl）基因。我们发现fstl 2是一个早期原肠胚表达的基因。它的失活，类似于nog 1，强烈增强冠心病表型。同时失活chd、nog 1和fstl 2时，腹侧化表型的突变率更高。总之，我们的数据表明，虽然Chordin是D/V轴的主要参与者，足以维持Bmp梯度的适当活性，但chd突变体中保留的结构（即背侧和背外侧区域，在中胚层和外胚层两者中）由Nog 1和Fst 12在囊胚和原肠胚阶段携带的抗BMP活性引起。(c)2006年爱思唯尔公司All rights reserved.
In Xenopus, the dorso-ventral (D/V) axis is thought to be specified by the bone morphogenetic proteins (Bmp) activity arising through interaction with antagonists such as Noggin, Chordin and Follistatin. We report here, through inactivation of noggin1 (nog1) that this gene is not essential by itself to establish the D/V patterning. However, at blastula stage, inactivation of nog1 strongly amplifies chordin (chd) phenotype, revealing redundant functions of these two genes on D/V axis formation. Substantial dorsal tissues remaining in the double nog1-chd morphant suggested that other anti-Bmp factors may pattern the D/V axis. We isolated two potential candidates, the follistatin-like (fstl) genes. We found that fstl2 is an early gastrula expressed gene. Its inactivation, similar to nog1, strongly enhances the chd phenotype. Moreover, the penetrance of the ventralization phenotype is much higher when we inactivated simultaneously chd, nog1 and fstl2.Altogether, our data reveal that, while Chordin is the main player of the D/V axis, sufficient to maintain proper activity of Bmp gradient, the structures remaining in the chd mutant (namely dorsal and dorso-lateral territories, in both mesodermal and ectodermal layers) result from the anti-Bmp activity carried by Nog1 and Fstl2 at blastula and gastrula stages. (c) 2006 Elsevier Inc. All rights reserved.