APOBEC2, a selective inhibitor of TGFβ signaling, regulates left-right axis specification during early embryogenesis.
APOBEC2, a selective inhibitor of TGFβ signaling, regulates left-right axis specification during early embryogenesis.
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APOBEC2 是TGFβ 信号传导的选择性抑制剂，在早期胚胎发生过程中调节左右轴规范。
DOI：
10.1016/j.ydbio.2010.09.016
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发表时间：
2011
影响因子：
2.7
通讯作者：
Brivanlou,AliH
中科院分区：
文献类型：
--
作者：
Vonica,Alin;Rosa,Alessandro;Arduini,BrigitteL;Brivanlou,AliH
左右不对称的规范是脊椎动物进化上保守的发育过程。两种 TGFβ 配体 Derrière/GDF1 和 Xnr1/Nodal 之间的相互作用，与 Lefty 和 Coco/Cerl2 等抑制剂一起，已被证明可以提供导致侧向性建立的信号。然而，导致和跟随这些信号的分子事件仍然大多未知。我们发现 APOBEC2 是 DNA/RNA 编辑酶胞苷脱氨酶家族的成员，由 TGFβ 信号传导诱导，并且其活性对于指定爪蟾和斑马鱼胚胎中的左右轴是必需的。令人惊讶的是，我们发现 APOBEC2 选择性抑制 Derrière 信号传导，但不抑制 Xnr1 信号传导。在哺乳动物成肌细胞系中，由于 APOBEC2 阻断 TGFβ 信号传导并促进肌肉分化，因此抑制作用是保守的。这首次证明一种假定的 RNA/DNA 编辑酶调节 TGFβ 信号传导并在发育中发挥重要作用。
The specification of left–right asymmetry is an evolutionarily conserved developmental process in vertebrates. The interplay between two TGFβ ligands, Derrière/GDF1 and Xnr1/Nodal, together with inhibitors such as Lefty and Coco/Cerl2, have been shown to provide the signals that lead to the establishment of laterality. However, molecular events leading to and following these signals remain mostly unknown. We find that APOBEC2, a member of the cytidine deaminase family of DNA/RNA editing enzymes, is induced by TGFβ signaling, and that its activity is necessary to specify the left–right axis in Xenopus and zebrafish embryos. Surprisingly, we find that APOBEC2 selectively inhibits Derrière, but not Xnr1, signaling. The inhibitory effect is conserved, as APOBEC2 blocks TGFβ signaling, and promotes muscle differentiation, in a mammalian myoblastic cell line. This demonstrates for the first time that a putative RNA/DNA editing enzyme regulates TGFβ signaling and plays a major role in development.