Unexpected activities of Smad7 in Xenopus mesodermal and neural induction
Unexpected activities of Smad7 in Xenopus mesodermal and neural induction
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DOI：
10.1016/j.mod.2008.02.002
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发表时间：
2008-05-01
影响因子：
2.6
通讯作者：
Linker, Claudia
中科院分区：
文献类型：
--
作者：
de Almeida, Irene;Rolo, Ana;Linker, Claudia
神经诱导被广泛认为是抑制BMP通路的直接结果。由于相互矛盾的结果和解释，我们在爪蟾和鸡胚胎中使用强大和通用的TGF β抑制剂Smad7重新检查了这一问题，Smad7抑制Smad1- (BMP)和Smad2-（节点/激活素）介导的途径。我们证实Smad7有效抑制Smad1和Smad2的磷酸化。然而，令人惊讶的是，Smad7在爪蟾腹侧表皮的过表达诱导了背侧中胚层标记物Chordin和Brachyury的表达。神经标记物被诱导，但以非细胞自主的方式，只有当Chordin和Brachyury也被诱导时。通过不同的方法同时抑制Smad1和Smad2并不能解释Smad7的所有作用，这表明Smad7除了抑制TGFb途径外还有其他活性。我们提供的证据表明，这些影响是独立于Wnt， FGF， Hedgehog和类视黄醛信号的。我们还表明，这些影响是由于Smad7的MH2结构域之外的元素。综上所述，这些结果表明，即使在节点/激活素也被阻断的情况下，BMP的抑制也不足以诱导神经，而且Smad7的活性比之前假设的要复杂得多。我们建议，在解释依赖Smad7作为TGF β途径抑制剂的实验时应相当谨慎。2008爱思唯尔爱尔兰有限公司版权所有。
Neural induction is widely believed to be a direct consequence of inhibition of BMP pathways. Because of conflicting results and interpretations, we have re-examined this issue in Xenopus and chick embryos using the powerful and general TGF beta inhibitor, Smad7, which inhibits both Smad1- (BMP) and Smad2- (Nodal/Activin) mediated pathways. We confirm that Smad7 efficiently inhibits phosphorylation of Smad1 and Smad2. Surprisingly, however, over-expression of Smad7 in Xenopus ventral epidermis induces expression of the dorsal mesodermal markers Chordin and Brachyury. Neural markers are induced, but in a noncell-autonomous manner and only when Chordin and Brachyury are also induced. Simultaneous inhibition of Smad1 and Smad2 by different approaches does not account for all Smad7 effects, indicating that Smad7 has activities other than inhibition of the TGFb pathway. We provide evidence that these effects are independent of Wnt, FGF, Hedgehog and retinoid signalling. We also show that these effects are due to elements outside of the MH2 domain of Smad7. Together, these results indicate that BMP inhibition is not sufficient for neural induction even when Nodal/Activin is also blocked, and that Smad7 activity is considerably more complex than had previously been assumed. We suggest that experiments relying on Smad7 as an inhibitor of TGF beta-pathways should be interpreted with considerable caution. (c) 2008 Elsevier Ireland Ltd. All rights reserved.