Complex functions of Mef2 splice variants in the differentiation of endoderm and of a neuronal cell type in a sea anemone
Complex functions of Mef2 splice variants in the differentiation of endoderm and of a neuronal cell type in a sea anemone
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DOI：
10.1242/dev.068122
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发表时间：
2011-11-15
期刊：
影响因子：
4.6
通讯作者：
Technau, Ulrich
中科院分区：
文献类型：
--
作者：
Genikhovich, Grigory;Technau, Ulrich
在三叶细胞动物中，中胚层产生许多组织和器官，包括肌肉。相比之下，双胚细胞门的代表动物（珊瑚、海葵、水母和水螅）缺乏中胚层，但拥有肌肉。在脊椎动物和昆虫中，转录因子 Mef2 在肌肉分化中发挥着关键作用。然而，它也是神经元分化和存活的重要调节因子。海葵 Nematostella vectensis 是一种缺乏中胚层但具有肌肉和神经元的生物体，据报道，Mef2 (Nvmef2) 存在于可能具有神经起源的单个外胚层细胞中。令我们惊讶的是，我们发现 Nvmef2 是选择性剪接的，形成差异表达的变体。使用吗啉介导的敲低和 mRNA 注射，我们证明 Nvmef2 的特定剪接变体是内胚层细胞的增殖和分化以及外胚层线虫细胞（一种神经元细胞类型）发育所必需的。此外，我们在反式激活结构域中发现了一个小的保守基序，该基序与 Nvmef2 的内胚层功能至关重要。反式激活结构域中关键且保守基序的鉴定预示着在脊椎动物 Mef2 功能中具有类似的重要作用。这是对双胚层动物中几种中胚层衍生物的决定因素的首次功能研究。我们的数据表明，Mef2 的选择性剪接变体在内中胚层和神经元分化中的参与早于刺胞动物-两侧对称动物的分裂。
In triploblastic animals, mesoderm gives rise to many tissues and organs, including muscle. By contrast, the representatives of the diploblastic phylum Cnidaria (corals, sea anemones, jellyfish and hydroids) lack mesoderm but possess muscle. In vertebrates and insects, the transcription factor Mef2 plays a pivotal role in muscle differentiation; however, it is also an important regulator of neuron differentiation and survival. In the sea anemone Nematostella vectensis, an organism that lacks mesoderm but has muscles and neurons, Mef2 (Nvmef2) has been reported in single ectodermal cells of likely neural origin. To our surprise, we found that Nvmef2 is alternatively spliced, forming differentially expressed variants. Using morpholino-mediated knockdown and mRNA injection, we demonstrate that specific splice variants of Nvmef2 are required for the proliferation and differentiation of endodermal cells and for the development of ectodermal nematocytes, a neuronal cell type. Moreover, we identified a small conserved motif in the transactivation domain that is crucially involved in the endodermal function of Nvmef2. The identification of a crucial and conserved motif in the transactivation domain predicts a similarly important role in vertebrate Mef2 function. This is the first functional study of a determinant of several mesodermal derivatives in a diploblastic animal. Our data suggest that the involvement of alternative splice variants of Mef2 in endomesoderm and neuron differentiation predates the cnidarian-bilaterian split.