ERK signaling pathway regulates embryonic survival and eye development in goldfish, Carassius auratus.
ERK signaling pathway regulates embryonic survival and eye development in goldfish, Carassius auratus.
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DOI：
10.2174/1566524011313090067
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发表时间：
2013-06
影响因子：
2.5
通讯作者：
L. Li;L. Wang;T-T Li-T;X. Li;X.–Q. Huang;X-W Chen;Z. Li;X. Lv;F-Y Liu;Z-W Luo;M. Liu;X-H Hu;W-F Hu;Z-X Huang;M. Yi;S. Liu;Y.-Z. Liu;D. W. Li
中科院分区：
文献类型：
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作者：
L. Li;L. Wang;T-T Li-T;X. Li;X.–Q. Huang;X-W Chen;Z. Li;X. Lv;F-Y Liu;Z-W Luo;M. Liu;X-H Hu;W-F Hu;Z-X Huang;M. Yi;S. Liu;Y.-Z. Liu;D. W. Li
细胞外信号调节激酶（ERK）是三种主要类型的丝裂原活化蛋白激酶之一。以往的研究表明，ERKs介导哺乳动物细胞增殖、分化、存活和转化的多种信号通路。在本研究中，我们以金鱼为模型系统，证明ERK激酶在促进脊椎动物胚胎存活和调节眼睛和躯干发育中发挥重要作用。ERKs在成年金鱼晶状体上皮细胞、晶状体纤维细胞、视网膜、脑、肌肉和心脏等多个组织中均有高表达。将ERK显性阴性突变体（DNM-ERK）注射到金鱼受精卵中，可显著抑制囊胚期ERK活性，完全阻断原肠期及后期ERK活性。结果表明，注射后的胚泡细胞被诱导凋亡，大部分胚胎在胚胎期死亡。在分子水平上，DNM-ERKs抑制ERK活性可抑制Bad在Ser-112位点的磷酸化，促进细胞凋亡。当U0126处理抑制MEK活性时，观察到类似的结果。存活的胚胎在眼和躯干表型上均表现出明显的异常。与眼发育异常相关，Pax-6磷酸化和HSF4表达显著降低，β-晶体蛋白基因表达下调。这些结果为ERKs在调节脊椎动物发育中的作用提供了新的信息。
The extracellular signal-regulated kinase (ERK) is one of the three major types of mitogen-activated protein kinases. Previous studies showed that ERKs mediate various signaling pathways for cell proliferation, differentiation, survival and transformation in mammals. In the present study, we use goldfish as a model system and demonstrate that ERK kinases play important roles in promoting embryonic survival and regulate development of eye and trunk in vertebrates. ERKs are highly expressed in multiple tissues including lens epithelial cells, lens fiber cells, retina, brain, muscle and heart of adult goldfish. Injection of the dominant negative ERK mutant (DNM-ERK) into the fertilized eggs of goldfish significantly inhibited ERK activity at blastula stage, and completely blocked ERK activity at gastrula and later stages. As a result, the blastula cells were induced into apoptosis, and majority of the injected embryos were lethal at embryonic stages. At the molecular level, inhibition of ERK activity by DNM-ERKs suppressed phosphorylation of Bad at Ser-112 to promote apoptosis. Similar results were observed when MEK activity was inhibited by U0126 treatment. The survived embryos display significant abnormality in the phenotypes of both eye and trunk. Associated with the abnormality in the eye development, phosphorylation in Pax-6 and expression of HSF4 were significantly decreased and expression of the β-crystallin gene was also downregulated. These results provide novel information regarding the roles of ERKs in regulating vertebrate development.