Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells
Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells
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DOI：
10.1111/j.1349-7006.2011.02104.x
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发表时间：
2012-01
期刊：
影响因子：
5.7
通讯作者：
Rika Saito;H. Nakauchi;Sumiko Watanabe
中科院分区：
文献类型：
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作者：
Rika Saito;H. Nakauchi;Sumiko Watanabe
丝氨酸/苏氨酸激酶Melk最初克隆于卵母细胞中，但它在正常组织中表达，尤其是在癌细胞中。我们先前已经确定Melk是在未成熟小鼠视网膜祖细胞中高度表达的基因。为了分析Melk在胚胎发生中的功能，我们克隆了斑马鱼Melk，并报道了斑马鱼中基于吗啉代的Melk下调导致严重贫血。Melk-吗啉代处理的斑马鱼也表现出小眼症，表明Melk参与视网膜发育。在Melk缺失的视网膜中，视网膜神经元分化发生但延迟，并且视网膜祖细胞的增殖期延长，这表明Melk可能调节从增殖向分化转变的时间。为了进行更详细的检查，我们在小鼠视网膜中进行了Melk功能获得和丧失分析。在小鼠胚胎视网膜外植体培养中，通过shRNA敲低Melk导致视网膜祖细胞的增殖活性降低，因此，Melk的过表达略微增强增殖。视网膜祖细胞分化为视网膜神经元亚型的影响并不显著，但Müller胶质细胞分化受到Melk水平的干扰。此外，神经胶质细胞的突起延伸在缺乏Melk的情况下增强，表明Melk参与视网膜细胞的形态分化。综上所述，我们的研究结果表明，Melk主要是必要的适当的增殖，并可能在脊椎动物的视网膜发育中发挥多种作用。（Cancer Sci 2012; 103：42-49）
Serine/threonine kinase, Melk, was initially cloned in oocytes, but it is expressed in normal tissues and especially in cancer cells. We had previously identified Melk as a gene that is highly expressed in immature mouse retinal progenitors. To analyze the function of Melk in embryogenesis, we cloned zebrafish Melk and reported that morpholino‐based downregulation of Melk in zebrafish resulted in severe anemia. Melk‐morpholino‐treated zebrafish also showed microphthalmia, suggesting the participation of Melk in retinal development. In Melk‐depleted retinas, differentiation of retinal neurons took place but was delayed, and the proliferative period of retinal progenitor cells was prolonged, suggesting that Melk might regulate the timing of the transition from proliferation to differentiation. For more detailed examination, we performed gain‐ and loss‐of‐function analyses of Melk in mouse retinas. Knockdown of Melk by shRNA in mouse embryonic retinal explant culture resulted in decreased proliferative activity of retinal progenitors, and accordingly, overexpression of Melk slightly enhanced proliferation. Differentiation of retinal progenitor into subtypes of retinal neurons was not significantly affected, but Müller glia differentiation was perturbed by the level of Melk. Furthermore, process extension of glial cells was enhanced in the absence of Melk, suggesting that Melk is involved in the morphological differentiation of retinal cells. Taken together, our results suggest that Melk is primarily required for proper proliferation, and might play multiple roles in retinal development in vertebrates. (Cancer Sci 2012; 103: 42–49)