Mecp2 regulates neural cell differentiation by suppressing the Id1 to Her2 axis in zebrafish
Mecp2 regulates neural cell differentiation by suppressing the Id1 to Her2 axis in zebrafish
复制标题
Mecp2 通过抑制斑马鱼的 Id1 至 Her2 轴来调节神经细胞分化。
DOI：
10.1242/jcs.167874
复制
发表时间：
2015-06-15
影响因子：
4
通讯作者：
Xiong, Jing-Wei
中科院分区：
文献类型：
--
作者：
Gao, Hai;Bu, Ye;Xiong, Jing-Wei
Rett综合征（RTT）是一种进行性神经系统疾病，由X连锁蛋白甲基-CpG结合蛋白2（MeCP 2）突变引起。MeCP 2在神经分化过程中的内源性功能尚不清楚。在这里，我们报告说mecp 2是斑马鱼大脑发育所必需的。Mecp 2最初在胚胎中广泛表达，后来在大脑中富集。mecp 2的morpholino敲除或基因缺失抑制神经元分化，而其过表达促进神经元分化，这表明mecp 2在指导神经前体细胞分化为分化的神经元中起重要作用。从机制上讲，her 2（哺乳动物Hes 5的斑马鱼直系同源物）在mecp 2 morphants中以Id 1依赖性方式上调。此外，her 2或id 1的敲除完全挽救了mecp 2变体的神经元分化。这些结果表明，Mecp 2通过抑制Id 1-Her 2轴在神经细胞发育中起着重要作用，并提供了新的证据，即胚胎神经缺陷导致RTT后期运动和认知功能障碍。
Rett syndrome (RTT) is a progressive neurological disorder caused by mutations in the X-linked protein methyl-CpG-binding protein 2 (MeCP2). The endogenous function of MeCP2 during neural differentiation is still unclear. Here, we report that mecp2 is required for brain development in zebrafish. Mecp2 was broadly expressed initially in embryos and enriched later in the brain. Either morpholino knockdown or genetic depletion of mecp2 inhibited neuronal differentiation, whereas its overexpression promoted neuronal differentiation, suggesting an essential role of mecp2 in directing neural precursors into differentiated neurons. Mechanistically, her2 (the zebrafish ortholog of mammalian Hes5) was upregulated in mecp2 morphants in an Id1-dependent manner. Moreover, knockdown of either her2 or id1 fully rescued neuronal differentiation in mecp2 morphants. These results suggest that Mecp2 plays an important role in neural cell development by suppressing the Id1-Her2 axis, and provide new evidence that embryonic neural defects contribute to the later motor and cognitive dysfunctions in RTT.