Zinc Finger DHHC-Type Containing 13 Regulates Fate Specification of Ectoderm and Mesoderm Cell Lineages by Modulating Smad6 Activity
Zinc Finger DHHC-Type Containing 13 Regulates Fate Specification of Ectoderm and Mesoderm Cell Lineages by Modulating Smad6 Activity
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含有 13 的锌指 DHHC 型通过调节 Smad6 活性来调节外胚层和中胚层细胞谱系的命运规范
DOI：
10.1089/scd.2014.0068
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发表时间：
2014-08-15
影响因子：
4
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
--
作者：
Chen, Xueran;Shi, Wei;Hao, Aijun
Asp-His-His-Cys（DHHC）蛋白在胚胎细胞命运规范中的作用尚未明确，其活性的潜在机制也未得到很好的理解。在这里，我们比较了锌指DHHC型（Zdhhc 13）在斑马鱼胚胎和体外细胞模型中的胚胎功能。Zdhhc 13是骨形态发生蛋白（BMP）信号传导的关键调节因子，其特异性结合于Smad 6，通过不依赖于其棕榈酰转移酶活性的机制诱导Smad 6在核周聚集和降解。我们发现，Zdhhc 13在斑马鱼胚胎发生过程中发挥了至关重要的作用，在控制胚层规格，特别是在外胚层和中胚层分化的稳态。Zdhhc 13的缺失导致斑马鱼胚胎外胚层神经化和中胚层背侧化。此外，在我们的体外细胞模型中，Zdhhc 13在BMP依赖性信号传导和早期谱系决定期间拮抗Smad 6。我们的研究结果扩展了Zdhhc 13的细胞作用，表明它在BMP信号传导中起调节剂的作用，并确定了Zdhhc 13的胚胎功能是在谱系特化中。
Neither the roles of Asp-His-His-Cys (DHHC)-containing proteins in embryonic cell fate specification are well defined, nor the underlying mechanisms of their activity are well understood. Here, we compared the embryonic function of zinc finger DHHC-type containing (Zdhhc13) in zebrafish embryos and in an in vitro cell model. Zdhhc13, a critical regulator of bone morphogenetic protein (BMP) signaling, specifically bound to Smad6 to induce its perinuclear accumulation and degradation through a mechanism independent of its palmitoyltransferase activity. We showed that Zdhhc13 played a crucial role during zebrafish embryogenesis in the control of germ layer specification, particularly in ectoderm and mesoderm differentiation homeostasis. Depletion of Zdhhc13 led to the neuralization of ectoderm and dorsalization of mesoderm in zebrafish embryos. Moreover, Zdhhc13 antagonized Smad6 during BMP-dependent signaling and early lineage decisions in our in vitro cell model. Our results extended the cellular role of Zdhhc13, suggesting that it acts as a regulator in BMP signaling, and established that the embryonic function of Zdhhc13 is in lineage specification.