DIXDC1 Promotes Retinoic Acid-Induced Neuronal Differentiation and Inhibits Gliogenesis in P19 Cells
DIXDC1 Promotes Retinoic Acid-Induced Neuronal Differentiation and Inhibits Gliogenesis in P19 Cells
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DOI：
10.1007/s10571-008-9295-9
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发表时间：
2009-02-01
影响因子：
4
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Jing, Xiao-Tang;Wu, Hai-Tao;Fan, Ming
人DIXDC 1基因是一个包含Dishevelled-Axin（DIX）结构域的基因家族成员，在Wnt信号转导和神经发育中起重要作用。本研究首次证实DIXDC 1的小鼠同源基因Ccd 1在胚胎发育神经系统中表达上调。进一步的研究表明，Ccd 1特异性表达于神经元，并与早期神经元标记物Tuj 1共定位。在RA诱导的胚胎癌P19细胞聚集和神经元分化过程中，Ccd 1、Wnt-1和N-cadherin的表达显著增加。DIXDC 1在P19细胞中的稳定过表达促进神经元分化。过表达DIXDC 1的P19细胞在RA诱导下仅2天即可分化为Tuj 1阳性细胞，而对照P19细胞则不能。同时，我们还发现过表达DIXDC 1分别促进了P19细胞聚集和分化过程中Wnt 1和bHLHs的表达，同时通过下调GFAP的表达来抑制胶质细胞的生成。DIXDC 1在胚胎癌P19细胞中过表达可促进神经元的分化，抑制视黄酸诱导的胶质细胞的形成。
Human DIXDC1 is a member of Dishevelled-Axin (DIX) domain containing gene family which plays important roles in Wnt signaling and neural development. In this report, we first confirmed that expression of Ccd1, a mouse homologous gene of DIXDC1, was up-regulated in embryonic developing nervous system. Further studies showed that Ccd1 was expressed specifically in neurons and colocalized with early neuronal marker Tuj1. During the aggregation induced by RA and neuronal differentiation of embryonic carcinoma P19 cells, expressions of Ccd1 as well as Wnt-1 and N-cadherin were dramatically increased. Stable overexpression of DIXDC1 in P19 cells promoted the neuronal differentiation. P19 cells over-expressing DIXDC1 but not the control P19 cells could differentiate into Tuj1 positive cells with RA induction for only 2 days. Meanwhile, we also found that overexpression of DIXDC1 facilitated the expression of Wnt1 and bHLHs during aggregation and differentiation, respectively, while inhibited gliogenesis by down-regulating the expression of GFAP in P19 cells. Thus, our finding suggested that DIXDC1 might play an important role during neurogenesis, overexpression of DIXDC1 in embryonic carcinoma P19 cells promoted neuronal differentiation, and inhibited gliogenesis induced by retinoic acid.