The RNA-binding protein HuD regulates neuronal cell identity and maturation
The RNA-binding protein HuD regulates neuronal cell identity and maturation
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DOI：
10.1073/pnas.0407523102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Okano, H
中科院分区：
文献类型：
--
作者：
Akamatsu, W;Fujihara, H;Okano, H
神经Hu蛋白（HuB/C/D）是一种rna结合蛋白，在未成熟的神经祖细胞或未分化的神经肿瘤中过度表达时，可诱导神经元分化活性。新生的hud缺陷小鼠在胚胎早期表现出短暂的脑神经发育受损表型。成年hud缺陷小鼠后肢反射异常，旋转能力差。对神经球形成的分析显示，hud缺陷小鼠神经干细胞/祖细胞的数量和自我更新能力增加。缺乏hud的初级神经球产生的神经元数量也较少。利用BrdUrd和碘脱氧尿嘧啶标记对细胞增殖活性进行队列分析，发现胚胎脑壁分化的静止细胞数量减少。长期给药BrdUrd显示，在hud缺陷小鼠中，成年室下区缓慢分裂的干细胞数量增加。综上所述，结果表明HuD在神经元发育的多个阶段都是必需的，包括对神经干/祖细胞的增殖活性和神经元细胞命运获得的负调控。
Neural Hu proteins (HuB/C/D) are RNA-binding proteins that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated neuronal tumors. Newly generated HuD-deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD-deficient mice exhibited an abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed that the number and self-renewal capacity of the neural stem/progenitor cells were increased in HuD-deficient mice. HuD-deficient primary neurospheres also generated a smaller number of neurons. Cohort analysis of the cellular proliferative activity by using BrdUrd and iododeoxuridine labeling revealed that the number of differentiating quiescent cells in the embryonic cerebral wall was decreased. Long-term administration of BrdUrd revealed that the number of slowly dividing stem cells in the adult subventricular zone was increased in the HuD-deficient mice. Taken together, the results suggest that HuD is required at multiple points during neuronal development, including negative regulation of proliferative activity and neuronal cell-fate acquisition of neural stem/progenitor cells.