The role and regulation of GDF11 in Smad2 activation during tailbud formation in the Xenopus embryo.
The role and regulation of GDF11 in Smad2 activation during tailbud formation in the Xenopus embryo.
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DOI：
10.1016/j.mod.2010.08.004
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发表时间：
2010-09
影响因子：
2.6
通讯作者：
Whitman, Malcolm
中科院分区：
文献类型：
--
作者：
Ho, Diana M.;Yeo, Chang-Yeol;Whitman, Malcolm
TGF β超家族配体对Smad 2的磷酸化在早期胚胎的轴向模式形成中的关键作用已被充分确立。然而，Smad 2信号在后神经胚胚胎模式中的调节和作用还不太清楚。虽然各种TGF β超家族配体涉及前后图案化的各个阶段，但已显示配体GDF 11在小鼠中的原肠胚后图案化中具有特定作用。小鼠GDF 11特异性地定位于发育中的尾部，并且对于正常的后部轴向图案化是必需的。成熟的GDF 11配体被其自身的前结构域抑制，并且该前结构域的胞外蛋白水解被认为是GDF 11活性所必需的。这种蛋白水解调节机制在体内胚胎发生过程中对Smad激活的贡献，以及对后部模式的发展的贡献，尚未被表征。我们在这里调查的作用非洲爪蟾GDF 11在激活Smad 2在发育过程中的尾芽期胚胎，这种激活在幼虫发育中的作用。我们还证明了BMP-1/Tolloid样蛋白酶的活性对于在原肠胚后发育期间Smad 2磷酸化的正常GDF 11依赖性激活是必需的。这些数据表明，GDF 11在尾芽期非洲爪蟾胚胎中Smad 2磷酸化的激活中具有核心作用，并提供了第一个证据，即BMP-1/Tolloid介导的前结构域切割对于GDF 11在体内的激活是重要的。
A key role for phosphorylation of Smad2 by TGFß superfamily ligands in the axial patterning of early embryos is well established. The regulation and role of Smad2 signaling in post-neurula embryonic patterning, however, is less well understood. While a variety of TGFß superfamily ligands are implicated in various stages of anterior-posterior patterning, the ligand GDF11 has been shown to have a particular role in post-gastrula patterning in the mouse. Mouse GDF11 is specifically localized to the developing tail and is essential for normal posterior axial patterning. Mature GDF11 ligand is inhibited by its own prodomain, and extracellular proteolysis of this prodomain is thought to be necessary for GDF11 activity. The contribution of this proteolytic regulatory mechanism to Smad activation during embryogenesis in vivo, and to the development of posterior pattern, has not been characterized. We investigate here the role of Xenopus GDF11 in the activation of Smad2 during the development of tailbud stage embryos, and the role of this activation in larval development. We also demonstrate that the activity of BMP-1/Tolloid -like proteases is necessary for the normal GDF11-dependent activation of Smad2 phosphorylation during post-gastrula development. These data demonstrate that GDF11 has a central role in the activation of Smad2 phosphorylation in tailbud stage Xenopus embryos, and provide the first evidence that BMP-1/Tolloid-mediated prodomain cleavage is important for activation of GDF11 in vivo.
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